Hentze, M. W., Castello, A., Schwarzl, T. & Preiss, T. A brave new world of RNA-binding proteins. Nat. Rev. Mol. Cell Biol. 19, 327–341 (2018).
Queiroz, R. M. L. et al. Comprehensive identification of RNA–protein interactions in any organism using orthogonal organic phase separation (OOPS). Nat. Biotechnol. 37, 169–178 (2019).
Perez-Perri, J. I. et al. Global analysis of RNA-binding protein dynamics by comparative and enhanced RNA interactome capture. Nat. Protoc. 16, 27–60 (2021).
Ray, D. et al. A compendium of RNA-binding motifs for decoding gene regulation. Nature 499, 172–177 (2013).
Chen, Y. G. & Hur, S. Cellular origins of dsRNA, their recognition and consequences. Nat. Rev. Mol. Cell Biol. 23, 286–301 (2022).
Wang, I. X. et al. Human proteins that interact with RNA/DNA hybrids. Genome Res. 28, 1405–1414 (2018).
Madhani, H. D. The frustrated gene: origins of eukaryotic gene expression. Cell 155, 744–749 (2013).
Keene, J. D. & Tenenbaum, S. A. Eukaryotic mRNPs may represent posttranscriptional operons. Mol. Cell 9, 1161–1167 (2002). This study presents the important concept that functionally related genes are regulated post-transcriptionally by specific mRNA-binding proteins.
He, S., Valkov, E., Cheloufi, S. & Murn, J. The nexus between RNA-binding proteins and their effectors. Nat. Rev. Genet. 24, 276–294 (2023).
Turner, M. & Diaz-Muñoz, M. D. RNA-binding proteins control gene expression and cell fate in the immune system. Nat. Immunol. 19, 120–129 (2018).
Lisy, S., Rothamel, K. & Ascano, M. RNA binding proteins as pioneer determinants of infection: protective, proviral, or both? Viruses 13, 2172 (2021).
Bermudez, Y., Hatfield, D. & Muller, M. A balancing act: the viral–host battle over RNA binding proteins. Viruses 16, 474 (2024).
Liepelt, A. et al. Identification of RNA-binding proteins in macrophages by interactome capture. Mol. Cell. Proteom. 15, 2699–2714 (2016).
Xu, M. et al. The thymocyte-specific RNA-binding protein Arpp21 provides TCR repertoire diversity by binding to the 3′-UTR and promoting Rag1 mRNA expression. Nat. Commun. 15, 2194 (2024).
Chen, P. et al. A Csde1–Strap complex regulates plasma cell differentiation by coupling mRNA translation and decay. Nat. Commun. 16, 2906 (2025).
Hoefig, K. P. et al. Defining the RBPome of primary T helper cells to elucidate higher-order Roquin-mediated mRNA regulation. Nat. Commun. 12, 5208 (2021).
Kafasla, P., Skliris, A. & Kontoyiannis, D. L. Post-transcriptional coordination of immunological responses by RNA-binding proteins. Nat. Immunol. 15, 492–502 (2014).
Shifrut, E. et al. Genome-wide CRISPR screens in primary human T cells reveal key regulators of immune function. Cell 175, 1958–1971.e15 (2018).
Dong, M. B. et al. Systematic immunotherapy target discovery using genome-scale in vivo CRISPR screens in CD8 T cells. Cell 178, 1189–1204.e23 (2019).
Lin, C.-P. et al. Multimodal stimulation screens reveal unique and shared genes limiting T cell fitness. Cancer Cell 42, 623–645.e10 (2024). Together with Volta et al. (2021), this study reveals the profound effect of selective translational control on T cell function.
Vinuesa, C. G. et al. A RING-type ubiquitin ligase family member required to repress follicular helper T cells and autoimmunity. Nature 435, 452–458 (2005).
Zhao, H. et al. Genome-wide fitness gene identification reveals roquin as a potent suppressor of CD8 T cell expansion and anti-tumor immunity. Cell Rep. 37, 110083 (2021).
Wei, J. et al. Targeting REGNASE-1 programs long-lived effector T cells for cancer therapy. Nature 168, 724–726 (2019).
Behrens, G. et al. Disrupting Roquin-1 interaction with Regnase-1 induces autoimmunity and enhances antitumor responses. Nat. Immunol. 22, 1563–1576 (2021).
Kakiuchi, N. et al. Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis. Nature 577, 260–265 (2020).
Nanki, K. et al. Somatic inflammatory gene mutations in human ulcerative colitis epithelium. Nature 577, 254–259 (2020).
Alfonso-Gonzalez, C. & Hilgers, V. (Alternative) transcription start sites as regulators of RNA processing. Trends Cell Biol. 34, 1018–1028 (2024).
Frankish, A. et al. GENCODE: reference annotation for the human and mouse genomes in 2023. Nucleic Acids Res. 51, D942–D949 (2022).
Mitschka, S. & Mayr, C. Context-specific regulation and function of mRNA alternative polyadenylation. Nat. Rev. Mol. Cell Biol. 23, 779–796 (2022).
Rodríguez-Molina, J. B., West, S. & Passmore, L. A. Knowing when to stop: transcription termination on protein-coding genes by eukaryotic RNAPII. Mol. Cell 83, 404–415 (2023).
Kjer-Hansen, P. & Weatheritt, R. J. The function of alternative splicing in the proteome: rewiring protein interactomes to put old functions into new contexts. Nat. Struct. Mol. Biol. 30, 1844–1856 (2023).
Peterson, M. L. Immunoglobulin heavy chain gene regulation through polyadenylation and splicing competition. Wiley Interdiscip. Rev. RNA 2, 92–105 (2011).
Osma-Garcia, I. C. et al. The RNA-binding protein HuR is required for maintenance of the germinal centre response. Nat. Commun. 12, 6556 (2021).
Osma-Garcia, I. C. et al. The RNA binding proteins TIA1 and TIAL1 promote Mcl1 mRNA translation to protect germinal center responses from apoptosis. Cell. Mol. Immunol. 20, 1063–1076 (2023).
Huang, H. et al. The RNA-binding protein hnRNP F is required for the germinal center B cell response. Nat. Commun. 14, 1731 (2023).
Subramani, P. G. et al. Conserved role of hnRNPL in alternative splicing of epigenetic modifiers enables B cell activation. EMBO Rep. 25, 2662–2697 (2024).
Monzon-Casanova, E. et al. The RNA-binding protein PTBP1 is necessary for B cell selection in germinal centers. Nat. Immunol. 19, 267–278 (2018).
Sasanuma, H., Ozawa, M. & Yoshida, N. RNA binding protein Ptbp1 is essential for BCR-mediated antibody production. Int. Immunol. 31, 157–166 (2018).
Wu, Z. et al. Memory T cell RNA rearrangement programmed by heterogeneous nuclear ribonucleoprotein hnRNPLL. Immunity 29, 863–875 (2008).
Cho, V. et al. The RNA-binding protein hnRNPLL induces a T cell alternative splicing program delineated by differential intron retention in polyadenylated RNA. Genome Biol. 15, R26 (2014).
Yabas, M., Yazicioglu, Y. F., Hoyne, G. F., Goodnow, C. C. & Enders, A. Loss of hnRNPLL-dependent splicing of Ptprc has no impact on B-cell development, activation and terminal differentiation into antibody-secreting cells. Immunol. Cell Biol. 99, 532–541 (2021).
Diaz-Muñoz, M. D. et al. The RNA-binding protein HuR is essential for the B cell antibody response. Nat. Immunol. 16, 415–425 (2015).
Monzón-Casanova, E. et al. Polypyrimidine tract-binding proteins are essential for B cell development. eLife 9 e53557 (2019).
Monzón-Casanova, E., Bates, K. J., Smith, C. W. J. & Turner, M. Essential requirement for polypyrimidine tract binding proteins 1 and 3 in the maturation and maintenance of mature B cells in mice. Eur. J. Immunol. 51, 2266–2273 (2021).
D’Angeli, V. et al. Polypyrimidine tract binding protein 1 regulates the activation of mouse CD8 T cells. Eur. J. Immunol. 52, 1058–1068 (2022).
Karginov, T. A. et al. Autoregulated splicing of TRA2β programs T cell fate in response to antigen-receptor stimulation. Science 385, eadj1979 (2024). This study shows the elegant functional demonstration of how splicing-mediated generation of specific transcript isoforms governs T cell immune responses.
Stoilov, P., Daoud, R., Nayler, O. & Stamm, S. Human tra2-beta1 autoregulates its protein concentration by influencing alternative splicing of its pre-mRNA. Hum. Mol. Genet. 13, 509–524 (2004).
Porta, J. L., Matus-Nicodemos, R., Valentín-Acevedo, A. & Covey, L. R. The RNA-binding protein, polypyrimidine tract-binding protein 1 (PTBP1) is a key regulator of CD4 T cell activation. PLoS ONE 11, e0158708 (2016).
Popović, B. et al. Time-dependent regulation of cytokine production by RNA binding proteins defines T cell effector function. Cell Rep. 42, 112419 (2023). This study identifies more than 130 RBPs interacting with the IFNG, TNF and IL2 3′ UTRs in human T cells, characterizing ELAVL1 as a promoter and ZFP36L1, ATXN2L and ZC3HAV1 as limiters of cytokine production.
Osma-Garcia, I. C. et al. Post-transcriptional regulation by TIA1 and TIAL1 controls the transcriptional program enforcing T cell quiescence. Preprint at bioRxiv https://doi.org/10.1101/2024.09.03.608755 (2024).
Karginov, T. A., Ménoret, A. & Vella, A. T. Optimal CD8+ T cell effector function requires costimulation-induced RNA-binding proteins that reprogram the transcript isoform landscape. Nat. Commun. 13, 3540 (2022).
Leppek, K. et al. Roquin promotes constitutive mRNA decay via a conserved class of stem-loop recognition motifs. Cell 153, 869–881 (2013).
Garg, A. et al. PIN and CCCH Zn-finger domains coordinate RNA targeting in ZC3H12 family endoribonucleases. Nucleic Acids Res. 49, gkab316 (2021).
Tants, J.-N., Oberstrass, L., Weigand, J. E. & Schlundt, A. Structure and RNA-binding of the helically extended Roquin CCCH-type zinc finger. Nucleic Acids Res. 52, 9838–9853 (2024).
Collart, M. A., Audebert, L. & Bushell, M. Roles of the CCR4–Not complex in translation and dynamics of co-translation events. Wiley Interdiscip. Rev. RNA 15, e1827 (2024).
Cui, X. et al. Regnase-1 and roquin nonredundantly regulate Th1 differentiation causing cardiac inflammation and fibrosis. J. Immunol. 199, 4066–4077 (2017).
Mino, T. et al. Regnase-1 and roquin regulate a common element in inflammatory mRNAs by spatiotemporally distinct mechanisms. Cell 161, 1058–1073 (2015).
Mino, T. et al. Translation-dependent unwinding of stem-loops by UPF1 licenses regnase-1 to degrade inflammatory mRNAs. Nucleic Acids Res. 47, 8838–8859 (2019).
Linterman, M. A. et al. Roquin differentiates the specialized functions of duplicated T cell costimulatory receptor genes CD28 and ICOS. Immunity 30, 228–241 (2009).
Vogel, K. U. et al. Roquin paralogs 1 and 2 redundantly repress the Icos and Ox40 costimulator mRNAs and control follicular helper T cell differentiation. Immunity 38, 655–668 (2013).
Pratama, A. et al. Roquin-2 shares functions with its paralog roquin-1 in the repression of mRNAs controlling T follicular helper cells and systemic inflammation. Immunity 38, 669–680 (2013).
Moore, M. J. et al. ZFP36 RNA-binding proteins restrain T-cell activation and anti-viral immunity. eLife 7, e33057 (2018).
Petkau, G. et al. The timing of differentiation and potency of CD8 effector function is set by RNA binding proteins. Nat. Commun. 13, 2274 (2022).
Cook, M. E. et al. The ZFP36 family of RNA binding proteins regulates homeostatic and autoreactive T cell responses. Sci. Immunol. 7, eabo0981 (2022).
Snyder, B. L. et al. Synergistic roles of tristetraprolin family members in myeloid cells in the control of inflammation. Life Sci. Alliance 7, e202302222 (2024).
Murakawa, Y. et al. RC3H1 post-transcriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-κB pathway. Nat. Commun. 6, 7367 (2015).
Tiedje, C. et al. The RNA-binding protein TTP is a global post-transcriptional regulator of feedback control in inflammation. Nucleic Acids Res. 44, gkw474 (2016).
Patial, S. et al. Enhanced stability of tristetraprolin mRNA protects mice against immune-mediated inflammatory pathologies. Proc. Natl Acad. Sci. USA 113, 1865–1870 (2016).
Choudhary, I. et al. Tristetraprolin overexpression in non-hematopoietic cells protects against acute lung injury in mice. Front. Immunol. 11, 2164 (2020).
Xu, B. et al. Regulated tristetraprolin overexpression dampens the development and pathogenesis of experimental autoimmune uveitis. Front. Immunol. 11, 583510 (2021).
Tanaka-Yano, M. et al. Tristetraprolin overexpression drives hematopoietic changes in young and middle-aged mice generating dominant mitigating effects on induced inflammation in murine models. Geroscience 46, 1271–1284 (2023).
Wang, E. et al. Surface antigen-guided CRISPR screens identify regulators of myeloid leukemia differentiation. Cell Stem Cell 28, 718–731.e6 (2021).
Sowinska, W. et al. The homeostatic function of Regnase-2 restricts neuroinflammation. FASEB J. 37, e22798 (2023).
Uehata, T. et al. Malt1-induced cleavage of regnase-1 in CD4+ helper T cells regulates immune activation. Cell 153, 1036–1049 (2013).
Jeltsch, K. M. et al. Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their cooperatively repressed targets to promote TH17 differentiation. Nat. Immunol. 15, 1079–1089 (2014).
Schmidt, H. et al. Unrestrained cleavage of Roquin-1 by MALT1 induces spontaneous T cell activation and the development of autoimmunity. Proc. Natl Acad. Sci. USA 120, e2309205120 (2023). TCR signal strength determines the extent of RC3H12A inactivation with the most potent signals leading to derepression of targets that promote TH17 differentiation.
Petkau, G. et al. Zfp36l1 establishes the high-affinity CD8 T-cell response by directly linking TCR affinity to cytokine sensing. Eur. J. Immunol. 54, 2350700 (2024). This study shows the amounts of ZFP36L1 expressed by activated T cells reflect the TCR affinity for peptide and subsequent responsiveness to IL-2.
Ross, E. A. et al. Dominant suppression of inflammation via targeted mutation of the mRNA destabilizing protein tristetraprolin. J. Immunol. 195, 265–276 (2015).
Smallie, T. et al. Dual-specificity phosphatase 1 and tristetraprolin cooperate to regulate macrophage responses to lipopolysaccharide. J. Immunol. 195, 277–288 (2015).
Bestehorn, A. et al. Cytoplasmic mRNA decay controlling inflammatory gene expression is determined by pre-mRNA fate decision. Mol. Cell 85, 742–755.e9 (2025). This study introduces a new concept into the field of RNA decay mediated by RNA-binding proteins whereby the cytoplasmic RNA decay is determined by RBP interaction with pre-mRNA in the nucleus.
Schmidlin, M. et al. The ARE-dependent mRNA-destabilizing activity of BRF1 is regulated by protein kinase B. EMBO J. 23, 4760–4769 (2004).
Yu, D. et al. Roquin represses autoimmunity by limiting inducible T-cell co-stimulator messenger RNA. Nature 450, 299–303 (2007).
Glasmacher, E. et al. Roquin binds inducible costimulator mRNA and effectors of mRNA decay to induce microRNA-independent post-transcriptional repression. Nat. Immunol. 11, 725–733 (2010).
Fu, M. & Blackshear, P. J. RNA-binding proteins in immune regulation: a focus on CCCH zinc finger proteins. Nat. Rev. Immunol. 17, 130–143 (2016).
O’Neil, J. D. et al. Gain-of-function mutation of tristetraprolin impairs negative feedback control of macrophages in vitro yet has overwhelmingly anti-inflammatory consequences in vivo. Mol. Cell. Biol. 37, e00536-16 (2017).
Coelho, M. A. et al. Oncogenic RAS signaling promotes tumor immunoresistance by stabilizing PD-L1 mRNA. Immunity 47, 1083–1099.e6 (2017).
Galloway, A. et al. RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence. Science 352, 453–459 (2016).
Kaehler, M. et al. ZFP36L1 plays an ambiguous role in the regulation of cell expansion and negatively regulates CDKN1A in chronic myeloid leukemia cells. Exp. Hematol. 99, 54–64.e7 (2021).
Alon, U. Network motifs: theory and experimental approaches. Nat. Rev. Genet. 8, 450–461 (2007).
Essig, K. et al. Roquin suppresses the PI3K-mTOR signaling pathway to inhibit T helper cell differentiation and conversion of Treg to Tfr cells. Immunity 47, 1067–1082.e12 (2017).
Sáenz-Narciso, B., Bell, S. E., Matheson, L. S., Venigalla, R. K. C. & Turner, M. ZFP36-family RNA-binding proteins in regulatory T cells reinforce immune homeostasis. Nat. Commun. 16, 4192 (2025).
Höfer, T., Krichevsky, O. & Altan-Bonnet, G. Competition for IL-2 between regulatory and effector T cells to chisel immune responses. Front. Immunol. 3, 268 (2012).
Busse, D. et al. Competing feedback loops shape IL-2 signaling between helper and regulatory T lymphocytes in cellular microenvironments. Proc. Natl Acad. Sci. USA 107, 3058–3063 (2010).
Mai, D. et al. Combined disruption of T cell inflammatory regulators Regnase-1 and Roquin-1 enhances antitumor activity of engineered human T cells. Proc. Natl Acad. Sci. USA 120, e2218632120 (2023).
Mai, D. et al. ZFP36 disruption is insufficient to enhance the function of mesothelin-targeting human CAR-T cells. Sci. Rep. 14, 3113 (2024).
Newman, R. et al. Maintenance of the marginal-zone B cell compartment specifically requires the RNA-binding protein ZFP36L1. Nat. Immunol. 18, 683–693 (2017).
Salerno, F. et al. Translational repression of pre-formed cytokine-encoding mRNA prevents chronic activation of memory T cells. Nat. Immunol. 19, 828–837 (2018). This study provides mechanistic insights for the concept of poised transcripts in memory T cells by identifying a non-redundant role of ZFP36L2 as a translational repressor.
Zandhuis, N. D. et al. Regulation of IFN-γ production by ZFP36L2 in T cells is time-dependent. Eur. J. Immunol. 54, e2451018 (2024).
Bowling, E. A. et al. Spliceosome-targeted therapies trigger an antiviral immune response in triple-negative breast cancer. Cell 184, 384–403.e21 (2021). This study finds that spliceosome inhibition leads to the generation of self-derived dsRNA, which triggers MDA5/IFIH1-mediated and DDX58/RIG-I-mediated IFN responses.
Zheng, R. et al. hnRNPM protects against the dsRNA-mediated interferon response by repressing LINE-associated cryptic splicing. Mol. Cell 84, 2087–2103.e8 (2024).
Wang, E. et al. Targeting an RNA-binding protein network in acute myeloid leukemia. Cancer Cell 35, 369–384.e7 (2019).
Singh, S. et al. RBM39 degrader invigorates natural killer cells to eradicate neuroblastoma despite cancer cell plasticity. Nat. Commun. 16, 8287 (2025).
Geng, G. et al. PTBP1 is necessary for dendritic cells to regulate T-cell homeostasis and antitumour immunity. Immunology 163, 74–85 (2021).
Jin, Z., Liang, F., Yang, J. & Mei, W. hnRNP I regulates neonatal immune adaptation and prevents colitis and colorectal cancer. PLoS Genet. 13, e1006672 (2017).
Milstead, R. A., Link, C. D., Xu, Z. & Hoeffer, C. A. TDP-43 knockdown in mouse model of ALS leads to dsRNA deposition, gliosis, and neurodegeneration in the spinal cord. Cereb. Cortex 33, 5808–5816 (2022).
LaRocca, T. J., Mariani, A., Watkins, L. R. & Link, C. D. TDP-43 knockdown causes innate immune activation via protein kinase R in astrocytes. Neurobiol. Dis. 132, 104514 (2019).
Dunker, W. et al. TDP-43 prevents endogenous RNAs from triggering a lethal RIG-I-dependent interferon response. Cell Rep. 35, 108976 (2021).
Chang, A. Y. et al. Modulation of SF3B1 in the pre-mRNA spliceosome induces a RIG-I-dependent type I IFN response. J. Biol. Chem. 297, 101277 (2021).
Fletcher, A. et al. A TRIM21-based bioPROTAC highlights the therapeutic benefit of HuR degradation. Nat. Commun. 14, 7093 (2023).
Rothamel, K. et al. ELAVL1 primarily couples mRNA stability with the 3′ UTRs of interferon-stimulated genes. Cell Rep. 35, 109178 (2021).
Debès, C. et al. Ageing-associated changes in transcriptional elongation influence longevity. Nature 616, 814–821 (2023).
He, J. et al. ZBP1 senses spliceosome stress through Z-RNA:DNA hybrid recognition. Mol. Cell 85, 1790–1805.e7 (2025).
Yang, Z.-H. et al. ZBP1 senses splicing aberration through Z-RNA to promote cell death. Mol. Cell 85, 1775–1789.e5 (2025).
Sampaio, N. G. et al. MDA5 guards against infection by surveying cellular RNA homeostasis. Preprint at Res. Sq. https://doi.org/10.21203/rs.3.rs-6466919/v1 (2025).
Gokhale, N. S. et al. Cellular RNA interacts with MAVS to promote antiviral signaling. Science 386, eadl0429 (2024). Together with Sampaio et al. (2025), this paper uses UV crosslinking to covalently link protein to RNA to demonstrate that MDA5 and MAVS interact directly with self-RNAs.
Heraud-Farlow, J. E. et al. GGNBP2 regulates MDA5 sensing triggered by self double-stranded RNA following loss of ADAR1 editing. Sci. Immunol. 9, eadk0412 (2024).
Borden, K., Culjkovic-Kraljacic, B. & Cowling, V. To cap it all off, again: dynamic capping and recapping of coding and non-coding RNAs to control transcript fate and biological activity. Cell Cycle 20, 1347–1360 (2021).
Avila-Bonilla, R. G. & Macias, S. The molecular language of RNA 5’ ends: guardians of RNA identity and immunity. RNA 30, 327–336 (2024).
Wolf, T. et al. Dynamics in protein translation sustaining T cell preparedness. Nat. Immunol. 21, 927–937 (2020).
Seedhom, M. O. et al. Paradox found: global accounting of lymphocyte protein synthesis. eLife 12, RP89015 (2024).
Galloway, A. et al. Upregulation of RNA cap methyltransferase RNMT drives ribosome biogenesis during T cell activation. Nucleic Acids Res. 49, 6722–6738 (2021).
Knop, K., Gomez-Moreira, C., Galloway, A., Ditsova, D. & Cowling, V. H. RAM is upregulated during T cell activation and is required for RNA cap formation and gene expression. Discov. Immunol. 3, kyad021 (2023).
Mattijssen, S., Welting, T. J. M. & Pruijn, G. J. M. RNase MRP and disease. Wiley Interdiscip. Rev. RNA 1, 102–116 (2010).
Zhou, B. et al. Coevolution of RNA and protein subunits in RNase P and RNase MRP, two RNA processing enzymes. J. Biol. Chem. 300, 105729 (2024).
Robertson, N. et al. A disease-linked lncRNA mutation in RNase MRP inhibits ribosome synthesis. Nat. Commun. 13, 649 (2022). This study demonstrates that the basis of an inherited immune deficiency is defective ribosome biogenesis by activated T cells.
Tan, T. C. J. et al. Suboptimal T-cell receptor signaling compromises protein translation, ribosome biogenesis, and proliferation of mouse CD8 T cells. Proc. Natl Acad. Sci. USA 114, E6117–E6126 (2017).
Liu, Y. et al. tRNA-m1A modification promotes T cell expansion via efficient MYC protein synthesis. Nat. Immunol. 23, 1433–1444 (2022).
Lelouard, H. et al. Regulation of translation is required for dendritic cell function and survival during activation. J. Cell Biol. 179, 1427–1439 (2007).
Ceppi, M. et al. Ribosomal protein mRNAs are translationally-regulated during human dendritic cells activation by LPS. Immunome Res. 5, 5 (2009).
Hipolito, V. E. B. et al. Enhanced translation expands the endo-lysosome size and promotes antigen presentation during phagocyte activation. PLoS Biol. 17, e3000535 (2019).
Kimber, R. et al. RNA helicase DDX1 regulates germinal centre selection and affinity maturation by promoting tRNA ligase activity. Preprint at bioRxiv https://doi.org/10.1101/2025.01.10.632317 (2025).
Pelletier, J. & Sonenberg, N. The organizing principles of eukaryotic ribosome recruitment. Annu. Rev. Biochem. 88, 307–335 (2019).
So, L. et al. Regulatory T cells suppress CD4+ effector T cell activation by controlling protein synthesis. J. Exp. Med. 220, e20221676 (2023).
Naineni, S. K., Robert, F., Nagar, B. & Pelletier, J. Targeting DEAD-box RNA helicases: the emergence of molecular staples. Wiley Interdiscip. Rev. RNA 14, e1738 (2022).
Screen, M. et al. RNA helicase EIF4A1-mediated translation is essential for the GC response. Life Sci. Alliance 7, e202302301 (2024).
Volta, V. et al. A DAP5/eIF3d alternate mRNA translation mechanism promotes differentiation and immune suppression by human regulatory T cells. Nat. Commun. 12, 6979 (2021). Together with Lin et al. (2024), this study reveals the profound effect of selective translational control on T cell function.
Grove, D. J., Russell, P. J. & Kearse, M. G. To initiate or not to initiate: a critical assessment of eIF2A, eIF2D, and MCT-1·DENR to deliver initiator tRNA to ribosomes. Wiley Interdiscip. Rev. RNA 15, e1833 (2024).
Anderson, R. et al. eIF2A-knockout mice reveal decreased life span and metabolic syndrome. FASEB J. 35, e21990 (2021).
Bohlen, J. et al. Human MCTS1-dependent translation of JAK2 is essential for IFN-γ immunity to mycobacteria. Cell 186, 5114–5134.e27 (2023). This paper shows the discovery and functional characterization of a genetic immunodeficiency caused by mutations in MCTS1, a translation reinitiation factor which results in loss of interferon-mediated immunity.
Chen, B. et al. DENR controls JAK2 translation to induce PD-L1 expression for tumor immune evasion. Nat. Commun. 13, 2059 (2022). This study shows that the MCTS1 partner protein DENR promotes JAK2 translation and the activity of the IFNγ signalling pathway.
Xu, Y. et al. Translation control of the immune checkpoint in cancer and its therapeutic targeting. Nat. Med. 25, 301–311 (2019).
Pakos-Zebrucka, K. et al. The integrated stress response. EMBO Rep. 17, 1374–1395 (2016).
Mukherjee, D., Bercz, L. S., Torok, M. A. & Mace, T. A. Regulation of cellular immunity by activating transcription factor 4. Immunol. Lett. 228, 24–34 (2020).
Conza, G. D., Ho, P.-C., Cubillos-Ruiz, J. R. & Huang, S. C.-C. Control of immune cell function by the unfolded protein response. Nat. Rev. Immunol. 23, 546–562 (2023).
Hu, F. et al. ORFLine: a bioinformatic pipeline to prioritise small open reading frames identifies candidate secreted small proteins from lymphocytes. Bioinform. Oxf. Engl. 37, btab339 (2021).
Ansari, S. A. et al. Integrative analysis of macrophage ribo-Seq and RNA-Seq data define glucocorticoid receptor regulated inflammatory response genes into distinct regulatory classes. Comput. Struct. Biotechnol. J. 20, 5622–5638 (2022).
Scheu, S. et al. Activation of the integrated stress response during T helper cell differentiation. Nat. Immunol. 7, 644–651 (2006).
Turner, M. Regulation and function of poised mRNAs in lymphocytes. BioEssays 45, e2200236 (2023).
Asada, N. et al. The integrated stress response pathway controls cytokine production in tissue-resident memory CD4+ T cells. Nat. Immunol. 26, 557–566 (2025).
Magg, V. et al. Turnover of PPP1R15A mRNA encoding GADD34 controls responsiveness and adaptation to cellular stress. Cell Rep. 43, 114069 (2024).
Ben-Asouli, Y., Banai, Y., Pel-Or, Y., Shir, A. & Kaempfer, R. Human interferon-γ mRNA autoregulates its translation through a pseudoknot that activates the interferon-inducible protein kinase PKR. Cell 108, 221–232 (2002).
Jurkin, J. et al. The mammalian tRNA ligase complex mediates splicing of XBP1 mRNA and controls antibody secretion in plasma cells. EMBO J. 33, 2922–2936 (2014).
Salerno, F. et al. An integrated proteome and transcriptome of B cell maturation defines poised activation states of transitional and mature B cells. Nat. Commun. 14, 5116 (2023).
Benhamron, S. et al. Regulated IRE1-dependent decay participates in curtailing immunoglobulin secretion from plasma cells. Eur. J. Immunol. 44, 867–876 (2014).
Tang, C.-H. A. et al. Phosphorylation of IRE1 at S729 regulates RIDD in B cells and antibody production after immunization. J. Cell Biol. 217, 1739–1755 (2018).
Cairrão, F. et al. Pumilio protects Xbp1 mRNA from regulated Ire1-dependent decay. Nat. Commun. 13, 1587 (2022).
Brenes, A. J., Lamond, A. I. & Cantrell, D. A. The immunological proteome resource. Nat. Immunol. 24, 731–731 (2023).
Liu, Y., Qu, L., Liu, Y., Roizman, B. & Zhou, G. G. PUM1 is a biphasic negative regulator of innate immunity genes by suppressing LGP2. Proc. Natl Acad. Sci. USA 114, E6902–E6911 (2017).
Fernández-Alfara, M. et al. Antitumor T-cell function requires CPEB4-mediated adaptation to chronic endoplasmic reticulum stress. EMBO J. 42, e111494 (2023). This study shows that CPEB4 acts in T cells to promote anti-tumour responses by enabling them to adapt to the increased ER stress that accompanies effector function.
Sun, H., Li, K., Liu, C. & Yi, C. Regulation and functions of non-m6A mRNA modifications. Nat. Rev. Mol. Cell Biol. 24, 714–731 (2023).
National Academies of Sciences, Engineering and Medicine. Charting a Future for Sequencing RNA and Its Modifications (The National Academies Press, 2024).
Chen, W., Gullett, J. M., Tweedell, R. E. & Kanneganti, T. Innate immune inflammatory cell death: PANoptosis and PANoptosomes in host defense and disease. Eur. J. Immunol. 53, e2250235 (2023).
Nichols, P. J., Krall, J. B., Henen, M. A., Vögeli, B. & Vicens, Q. Z-RNA biology: a central role in the innate immune response? RNA 29, 273–281 (2023).
de Reuver, R. & Maelfait, J. Novel insights into double-stranded RNA-mediated immunopathology. Nat. Rev. Immunol. 24, 235–249 (2024).
Zhang, Y. et al. 5-Methylcytosine (m5C) RNA modification controls the innate immune response to virus infection by regulating type I interferons. Proc. Natl Acad. Sci. USA 119, e2123338119 (2022).
Peng, J. et al. Clinical implications of a new DDX58 pathogenic variant that causes lupus nephritis due to RIG-I hyperactivation. J. Am. Soc. Nephrol. 34, 258–272 (2023).
Lee, S. et al. DDX58 is associated with susceptibility to severe influenza virus infection in children and adolescents. J. Infect. Dis. 226, 2030–2036 (2022).
Han, D. & Xu, M. M. RNA modification in the immune system. Annu. Rev. Immunol. 41, 73–98 (2023).
Fagre, C. & Gilbert, W. Beyond reader proteins: RNA binding proteins and RNA modifications in conversation to regulate gene expression. Wiley Interdiscip. Rev. RNA 15, e1834 (2024).
Roost, C. et al. Structure and thermodynamics of N6-methyladenosine in RNA: a spring-loaded base modification. J. Am. Chem. Soc. 137, 2107–2115 (2015).
Liu, B. et al. A quantitative model predicts how m6A reshapes the kinetic landscape of nucleic acid hybridization and conformational transitions. Nat. Commun. 12, 5201 (2021).
Gao, Y. et al. m6A modification prevents formation of endogenous double-stranded RNAs and deleterious innate immune responses during hematopoietic development. Immunity 52, 1007–1021.e8 (2020).
Qiu, W. et al. N6-methyladenosine RNA modification suppresses antiviral innate sensing pathways via reshaping double-stranded RNA. Nat. Commun. 12, 1582 (2021).
Xiao, Z. et al. METTL3-mediated m6A methylation orchestrates mRNA stability and dsRNA contents to equilibrate γδ T1 and γδ T17 cells. Cell Rep. 42, 112684 (2023).
Guirguis, A. A. et al. Inhibition of METTL3 results in a cell-intrinsic interferon response that enhances antitumor immunity. Cancer Discov. 13, 2228–2247 (2023).
Winkler, R. et al. m6A modification controls the innate immune response to infection by targeting type I interferons. Nat. Immunol. 20, 173–182 (2019).
Wang, A. et al. m6A modifications regulate intestinal immunity and rotavirus infection. eLife 11, e73628 (2022).
Ge, X. et al. The loss of YTHDC1 in gut macrophages exacerbates inflammatory bowel disease. Adv. Sci. 10, 2205620 (2023). This study demonstrates the effect of RNA modification on translation of specific proteins, which affect antitumour immunity, and highlights an underappreciated role of RBPs and RNA modifications on antitumour responses mediated by APCs.
Leoni, C., Bataclan, M., Ito-Kureha, T., Heissmeyer, V. & Monticelli, S. The mRNA methyltransferase Mettl3 modulates cytokine mRNA stability and limits functional responses in mast cells. Nat. Commun. 14, 3862 (2023).
Han, D. et al. Anti-tumour immunity controlled through mRNA m6A methylation and YTHDF1 in dendritic cells. Nature 566, 270–274 (2019).
Li, H.-B. et al. m6A mRNA methylation controls T cell homeostasis by targeting the IL-7/STAT5/SOCS pathways. Nature 979, 81 (2017).
Yao, Y. et al. METTL3-dependent m6A modification programs T follicular helper cell differentiation. Nat. Commun. 12, 1333 (2021).
Ito-Kureha, T. et al. The function of Wtap in N6-adenosine methylation of mRNAs controls T cell receptor signaling and survival of T cells. Nat. Immunol. 23, 1208–1221 (2022).
Ito-Kureha, T. & Heissmeyer, V. Critical functions of N6-adenosine methylation of mRNAs in T cells. Biochim. Biophys. Acta Mol. Cell Res. 1870, 119380 (2023).
Lee, S., Hirota, K., Schuette, V., Fujita, T. & Kato, H. Attenuation of regulatory T cell function by type I IFN signaling in an MDA5 gain-of-function mutant mouse model. Biochem. Biophys. Res. Commun. 629, 171–175 (2022).
Luca, D. et al. Aberrant RNA sensing in regulatory T cells causes systemic autoimmunity. Sci. Adv. 10, eadk0820 (2024).
Tong, J. et al. m6A mRNA methylation sustains Treg suppressive functions. Cell Res. 6, 160003 (2018). Together with Lee et al. (2022) and Luca et al. (2024), this paper indicates the negative effect of sensing misfolded RNAs on the function of Treg cells.
Knebel, U. E. et al. Disrupted RNA editing in beta cells mimics early-stage type 1 diabetes. Cell Metab. 36, 48–61.e6 (2024). This paper provides evidence to suggest that misfolded RNAs trigger toxic interferon responses in insulin-secreting cells.
Jesus, D. F. D. et al. Redox regulation of m6A methyltransferase METTL3 in β-cells controls the innate immune response in type 1 diabetes. Nat. Cell Biol. 26, 421–437 (2024). This study shows how oxidative stress impairs the ability of the METTL3 enzyme to protect β-cells of the islets of Langerhans from a toxic IFN response.
Wilinski, D. & Dus, M. N6-adenosine methylation controls the translation of insulin mRNA. Nat. Struct. Mol. Biol. 30, 1260–1264 (2023).
Zaccara, S. & Jaffrey, S. R. A unified model for the function of YTHDF proteins in regulating m6A-modified mRNA. Cell 181, 1582–1595.e18 (2020).
Zou, Z. & He, C. The YTHDF proteins display distinct cellular functions on m6A-modified RNA. Trends Biochem. Sci. 49, 611–621 (2024).
Terajima, H. et al. N6-methyladenosine promotes induction of ADAR1-mediated A-to-I RNA editing to suppress aberrant antiviral innate immune responses. PLoS Biol. 19, e3001292 (2021).
Wang, L. et al. YTHDF2 inhibition potentiates radiotherapy antitumor efficacy. Cancer Cell 41, 1294–1308.e8 (2023).
Xiao, S. et al. The tumor-intrinsic role of the m6A reader YTHDF2 in regulating immune evasion. Sci. Immunol. 9, eadl2171 (2024).
Mapperley, C. et al. The mRNA m6A reader YTHDF2 suppresses proinflammatory pathways and sustains hematopoietic stem cell function. J. Exp. Med. 218, e20200829 (2020).
Ma, S. et al. YTHDF2 orchestrates tumor-associated macrophage reprogramming and controls antitumor immunity through CD8+ T cells. Nat. Immunol. 24, 255–266 (2023).
Zhang, L. et al. YTHDF2/m6A/NF-κB axis controls anti-tumor immunity by regulating intratumoral Tregs. EMBO J. 42, e113126 (2023).
Ma, S. et al. The RNA m6A reader YTHDF2 controls NK cell antitumor and antiviral immunity. J. Exp. Med. 218, e20210279 (2021).
Grenov, A. C. et al. The germinal center reaction depends on RNA methylation and divergent functions of specific methyl readers. J. Exp. Med. 218, e20210360 (2021).
Grenov, A., Hezroni, H., Lasman, L., Hanna, J. H. & Shulman, Z. YTHDF2 suppresses the plasmablast genetic program and promotes germinal center formation. Cell Rep. 39, 110778 (2022).
Turner, D. J. et al. A functional screen of RNA binding proteins identifies genes that promote or limit the accumulation of CD138+ plasma cells. eLife 11, e72313 (2022).
Huang, H. et al. Mettl14-mediated m6A modification is essential for germinal center B cell response. J. Immunol. 208, 1924–1936 (2022).
Huang, H. et al. Recognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation. Nat. Cell Biol. 20, 285–295 (2018).
Singh, V. et al. The mRNA-binding protein IGF2BP1 maintains intestinal barrier function by up-regulating occludin expression. J. Biol. Chem. 295, 8602–8612 (2020).
Bechara, R. et al. The RNA binding protein IMP2 drives a stromal-Th17 cell circuit in autoimmune neuroinflammation. JCI Insight 7, e152766 (2021).
Bechara, R. et al. The m6A reader IMP2 directs autoimmune inflammation through an IL-17- and TNFα-dependent C/EBP transcription factor axis. Sci. Immunol. 6 eabd1287 (2021). Together with Bechara et al. (2021), this paper shows that the RBP IGF-2 mRNA-binding protein-2 using mouse models, which bind to m6A-modified mRNAs, have an important role in promoting pathological immune responses including autoantibody-induced glomerulonephritis and experimental autoimmune encephalomyelitis.
Wang, S. et al. Enhancement of LIN28B-induced hematopoietic reprogramming by IGF2BP3. Genes Dev. 33, 1048–1068 (2019).
Yu, K.-H. et al. The phenotypical implications of immune dysregulation in fragile X syndrome. Eur. J. Neurol. 27, 590–593 (2020).
Edupuganti, R. R. et al. N6-methyladenosine (m6A) recruits and repels proteins to regulate mRNA homeostasis. Nat. Struct. Mol. Biol. 24, 870–878 (2017).
O’Connor, R. M. et al. A Drosophila model of fragile X syndrome exhibits defects in phagocytosis by innate immune cells. J. Cell Biol. 216, 595–605 (2017).
Zeng, Q. et al. Aberrant hyperexpression of the RNA binding protein FMRP in tumors mediates immune evasion. Science 378, eabl7207 (2022).
Garnon, J. et al. Fragile X-related protein FXR1P regulates proinflammatory cytokine tumor necrosis factor expression at the post-transcriptional level. J. Biol. Chem. 280, 5750–5763 (2005).
Xiang, J.-F. et al. N6-methyladenosines modulate A-to-I RNA editing. Mol. Cell 69, 126–135.e6 (2018).
Zhang, T. et al. ADAR1 masks the cancer immunotherapeutic promise of ZBP1-driven necroptosis. Nature 606, 594–602 (2022).
Gannon, H. S. et al. Identification of ADAR1 adenosine deaminase dependency in a subset of cancer cells. Nat. Commun. 9, 5450 (2018).
Liu, H. et al. Tumor-derived IFN triggers chronic pathway agonism and sensitivity to ADAR loss. Nat. Med. 25, 95–102 (2019).
Dorrity, T. J. et al. Long 3′UTRs predispose neurons to inflammation by promoting immunostimulatory double-stranded RNA formation. Sci. Immunol. 8, eadg2979 (2023). This study identifies long 3′ UTRs generated by the actions of the ELAVL family of RBPs in neurons as sources of immunostimulatory dsRNAs, which damage neurons lacking ADAR1.
Corbet, G. A., Burke, J. M. & Parker, R. Nucleic acid–protein condensates in innate immune signaling. EMBO J. 42, e111870 (2022).
Burke, J. M. Regulation of ribonucleoprotein condensates by RNase L during viral infection. Wiley Interdiscip. Rev. RNA 14, e1770 (2023).
Ripin, N. & Parker, R. Formation, function, and pathology of RNP granules. Cell 186, 4737–4756 (2023).
Hirose, T., Ninomiya, K., Nakagawa, S. & Yamazaki, T. A guide to membraneless organelles and their various roles in gene regulation. Nat. Rev. Mol. Cell Biol. 24, 288–304 (2023).
Corbet, G. A., Burke, J. M., Bublitz, G. R., Tay, J. W. & Parker, R. dsRNA-induced condensation of antiviral proteins modulates PKR activity. Proc. Natl Acad. Sci. USA 119, e2204235119 (2022).
Zappa, F. et al. Signaling by the integrated stress response kinase PKR is fine-tuned by dynamic clustering. J. Cell Biol. 221, e202111100 (2022).
Ma, W. & Mayr, C. A membraneless organelle associated with the endoplasmic reticulum enables 3′UTR-mediated protein–protein interactions. Cell 175, 1492–1506.e19 (2018).
Horste, E. L. et al. Subcytoplasmic location of translation controls protein output. Mol. Cell 83, 4509–4523.e11 (2023).
Lee, J. E., Cathey, P. I., Wu, H., Parker, R. & Voeltz, G. K. Endoplasmic reticulum contact sites regulate the dynamics of membraneless organelles. Science 367, eaay7108 (2020).
Child, J. R., Chen, Q., Reid, D. W., Jagannathan, S. & Nicchitta, C. V. Recruitment of endoplasmic reticulum-targeted and cytosolic mRNAs into membrane-associated stress granules. RNA 27, 1241–1256 (2021).
Curdy, N. et al. The proteome and transcriptome of stress granules and P bodies during human T lymphocyte activation. Cell Rep. 42, 112211 (2023). A comprehensive proteomic analysis of sorted P-bodies and stress granules from human T cells identified hundreds of proteins, most of which were shared and provided evidence for activation-induced remodelling of RNPs.
Tavernier, S. J. et al. A human immune dysregulation syndrome characterized by severe hyperinflammation with a homozygous nonsense Roquin-1 mutation. Nat. Commun. 10, 4779 (2019).
Franks, T. M. & Lykke-Andersen, J. TTP and BRF proteins nucleate processing body formation to silence mRNAs with AU-rich elements. Genes Dev. 21, 719–735 (2007).
Blanco, F. F., Sanduja, S., Deane, N. G., Blackshear, P. J. & Dixon, D. A. Transforming growth factor β regulates P-body formation through induction of the mRNA decay factor tristetraprolin. Mol. Cell. Biol. 34, 180–195 (2014).
Lumb, J. H. et al. DDX6 represses aberrant activation of interferon-stimulated genes. Cell Rep. 20, 819–831 (2017).
Choi, H. et al. Targeting DDX3X triggers antitumor immunity via a dsRNA-mediated tumor-intrinsic type I interferon response. Cancer Res. 81, 3607–3620 (2021).
Murayama, T. et al. Targeting DHX9 triggers tumor-intrinsic interferon response and replication stress in small cell lung cancer. Cancer Discov. 14, 468–491 (2024).
Burgess, H. M. & Mohr, I. Cellular 5′-3′ mRNA exonuclease Xrn1 controls double-stranded RNA accumulation and anti-viral responses. Cell Host Microbe 17, 332–344 (2015).
Zou, T. et al. XRN1 deletion induces PKR-dependent cell lethality in interferon-activated cancer cells. Cell Rep. 43, 113600 (2024).
Hosseini, A. et al. Retroelement decay by the exonuclease XRN1 is a viral mimicry dependency in cancer. Cell Rep. 43, 113684 (2024).
Ran, X.-B. et al. Targeting RNA exonuclease XRN1 potentiates efficacy of cancer immunotherapy. Cancer Res. 83, 922–938 (2023).
Ripin, N., Vasconcelos, L. M., de Ugay, D. A. & Parker, R. DDX6 modulates P-body and stress granule assembly, composition, and docking. J. Cell Biol. 223, e202306022 (2024).
Brothers, W. R., Ali, F., Kajjo, S. & Fabian, M. R. The EDC4-XRN1 interaction controls P-body dynamics to link mRNA decapping with decay. EMBO J. 42, e113933 (2023).
Suñer, C. et al. Macrophage inflammation resolution requires CPEB4-directed offsetting of mRNA degradation. eLife 11, e75873 (2022).
Herman, A. B. et al. Regulation of stress granule formation by inflammation, vascular injury, and atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 39, 2014–2027 (2019).
Place, D. E., Samir, P., Malireddi, R. S. & Kanneganti, T.-D. Integrated stress response restricts macrophage necroptosis. Life Sci. Alliance 5, e202101260 (2022).
Salerno, F., Turner, M. & Wolkers, M. C. Dynamic post-transcriptional events governing CD8+ T cell homeostasis and effector function. Trends Immunol. 41, 240–254 (2019).
Mollet, S. et al. Translationally repressed mRNA transiently cycles through stress granules during stress. Mol. Biol. Cell 19, 4469–4479 (2008).
Mateju, D. et al. Single-molecule imaging reveals translation of mRNAs localized to stress granules. Cell 183, 1801–1812.e13 (2020).
Bussi, C. et al. Stress granules plug and stabilize damaged endolysosomal membranes. Nature 623, 1062–1069 (2023). Stress granules plug holes in lysosomes to facilitate repair and in macrophages to hamper the replication of Mycobacterium tuberculosis.
Jia, J. et al. Stress granules and mTOR are regulated by membrane atg8ylation during lysosomal damage. J. Cell Biol. 221, e202207091 (2022).
Paget, M. et al. Stress granules are shock absorbers that prevent excessive innate immune responses to dsRNA. Mol. Cell 83, 1180–1196.e8 (2023). Stress granules limit activation of the innate immune system and protect cells from toxic IFN responses and cell death.
Voyer, T. L. et al. Inherited deficiency of stress granule ZNFX1 in patients with monocytosis and mycobacterial disease. Proc. Natl Acad. Sci. USA 118, e2102804118 (2021).
Vavassori, S. et al. Multisystem inflammation and susceptibility to viral infections in human ZNFX1 deficiency. J. Allergy Clin. Immunol. 148, 381–393 (2021).
Wang, Y. et al. Mitochondria-localised ZNFX1 functions as a dsRNA sensor to initiate antiviral responses through MAVS. Nat. Cell Biol. 21, 1346–1356 (2019).
Liu, H. et al. ZNFX1 promotes AMPK-mediated autophagy against Mycobacterium tuberculosis by stabilizing mRNA. JCI Insight 9, e171850 (2023).
Law, L. M. J. et al. ZAP’s stress granule localization is correlated with its antiviral activity and induced by virus replication. PLoS Pathog. 15, e1007798 (2019).
Kmiec, D., Lista, M. J., Ficarelli, M., Swanson, C. M. & Neil, S. J. D. S-farnesylation is essential for antiviral activity of the long ZAP isoform against RNA viruses with diverse replication strategies. PLoS Pathog. 17, e1009726 (2021).
Schwerk, J. et al. RNA-binding protein isoforms ZAP-S and ZAP-L have distinct antiviral and immune resolution functions. Nat. Immunol. 20, 1610–1620 (2019).
Wickenhagen, A. et al. A prenylated dsRNA sensor protects against severe COVID-19. Science 374, eabj3624 (2021). Together with Soveg et al. (2021), this paper identifies the tethering of the p46 OAS-1 dsRNA-binding protein to endomembranes to be critical for an efficient interferon response and disease resilience following viral infection.
Soveg, F. W. et al. Endomembrane targeting of human OAS1 p46 augments antiviral activity. eLife 10, e71047 (2021).
Wu, S. et al. 2′-5′-Oligoadenylate synthetase 1 polymorphisms are associated with tuberculosis: a case–control study. BMC Pulm. Med. 18, 180 (2018).
Li, H. et al. Identification of a Sjögren’s syndrome susceptibility locus at OAS1 that influences isoform switching, protein expression, and responsiveness to type I interferons. PLoS Genet. 13, e1006820 (2017).
Harioudh, M. K. et al. Oligoadenylate synthetase 1 displays dual antiviral mechanisms in driving translational shutdown and protecting interferon production. Immunity 57, 446–461.e7 (2024). This study demonstrates a dual role of OAS1 in protecting interferon pathway genes while inhibiting translation of viral RNAs. It reveals a connection of the OAS1 antiviral pathway to the canonical RNA decay machinery mediated by AU-rich element binding proteins.
Harioudh, M. K. et al. The canonical antiviral protein oligoadenylate synthetase 1 elicits antibacterial functions by enhancing IRF1 translation. Immunity 57, 1812–1827.e7 (2024).
McGuire, V. A. et al. Beta interferon production is regulated by p38 mitogen-activated protein kinase in macrophages via both MSK1/2- and tristetraprolin-dependent pathways. Mol. Cell. Biol. 37, e00454-16 (2017).
Sauer, I. et al. Interferons limit inflammatory responses by induction of tristetraprolin. Blood 107, 4790–4797 (2006).
Chang, L., Shav-Tal, Y., Trcek, T., Singer, R. H. & Goldman, R. D. Assembling an intermediate filament network by dynamic cotranslation. J. Cell Biol. 172, 747–758 (2006).
Chouaib, R. et al. A dual protein-mRNA localization screen reveals compartmentalized translation and widespread co-translational RNA targeting. Dev. Cell 54, 773–791.e5 (2020).
Burke, J. M., Ratnayake, O. C., Watkins, J. M., Perera, R. & Parker, R. G3BP1-dependent condensation of translationally inactive viral RNAs antagonizes infection. Sci. Adv. 10, eadk8152 (2024). This study is an intriguing study describing the role of RNP macroassemblies in limiting viral replication by trapping viral RNA and inhibiting its translation, which is countered by viral escape mechanisms, highlighting the coevolution of these processes.
Zhou, Y. et al. RNA damage compartmentalization by DHX9 stress granules. Cell 187, 1701–1718.e28 (2024).
Min, H. et al. Mesenchymal stromal cells reprogram monocytes and macrophages with processing bodies. STEM CELLS 39, 115–128 (2021).
Liedmann, S. et al. Localization of a TORC1-eIF4F translation complex during CD8+ T cell activation drives divergent cell fate. Mol. Cell 82, 2401–2414.e9 (2022).
Pua, H. H. et al. Increased hematopoietic extracellular RNAs and vesicles in the lung during allergic airway responses. Cell Rep. 26, 933–944.e4 (2019).
Céspedes, P. F. et al. T-cell trans-synaptic vesicles are distinct and carry greater effector content than constitutive extracellular vesicles. Nat. Commun. 13, 3460 (2022).
King, K. E., Ghosh, P. & Wozniak, A. L. TRIM25 dictates selective miRNA loading into extracellular vesicles during inflammation. Sci. Rep. 13, 22952 (2023).
Krawczyk, P. S. et al. Re-adenylation by TENT5A enhances efficacy of SARS-CoV-2 mRNA vaccines. Nature 641, 984–992 (2025).
Krienke, C. et al. A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis. Science 371, 145–153 (2021).
Foord, C. et al. The variables on RNA molecules: concert or cacophony? Answers in long-read sequencing. Nat. Methods 20, 20–24 (2023).
Inamo, J. et al. Long-read sequencing for 29 immune cell subsets reveals disease-linked isoforms. Nat. Commun. 15, 4285 (2024).
Pardo-Palacios, F. J. et al. Systematic assessment of long-read RNA-seq methods for transcript identification and quantification. Nat. Methods 21, 1349–1363 (2024).
Bilska, A. et al. Immunoglobulin expression and the humoral immune response is regulated by the non-canonical poly(A) polymerase TENT5C. Nat. Commun. 11, 2032–17 (2020).
Liudkovska, V. et al. TENT5 cytoplasmic noncanonical poly(A) polymerases regulate the innate immune response in animals. Sci. Adv. 8, eadd9468 (2022).
Tang, A. D. et al. Detecting haplotype-specific transcript variation in long reads with FLAIR2. Genome Biol. 25, 173 (2024).
Gupta, P., O’Neill, H., Wolvetang, E. J., Chatterjee, A. & Gupta, I. Advances in single-cell long-read sequencing technologies. NAR Genom. Bioinform. 6, lqae047 (2024).
Chekulaeva, M. Mechanistic insights into the basis of widespread RNA localization. Nat. Cell Biol. 26, 1037–1046 (2024).
Villanueva, E. et al. System-wide analysis of RNA and protein subcellular localization dynamics. Nat. Methods 21, 60–71 (2023).
Barna, M. et al. The promises and pitfalls of specialized ribosomes. Mol. Cell 82, 2179–2184 (2022).
Gao, Y. & Wang, H. Ribosome heterogeneity in development and disease. Front. Cell Dev. Biol. 12, 1414269 (2024).
Chai, P., Lebedenko, C. G. & Flynn, R. A. RNA crossing membranes: systems and mechanisms contextualizing extracellular RNA and cell surface glycoRNAs. Annu. Rev. Genom. Hum. Genet. 24, 85–107 (2023).
Zhang, N. et al. Cell surface RNAs control neutrophil recruitment. Cell 187, 846–860.e17 (2024). Cell-surface sialic acid containing glycoRNAs on neutrophils interacts with P-selectin on endothelial cells to promote neutrophil recruitment into sites of inflammation in vivo.
Cordes, J., Zhao, S., Engel, C. M. & Stingele, J. Cellular responses to RNA damage. Cell 188, 885–900 (2025).
Cao, X., Zhang, Y., Ding, Y. & Wan, Y. Identification of RNA structures and their roles in RNA functions. Nat. Rev. Mol. Cell Biol. 25, 784–801 (2024).
Tieu, V. et al. A versatile CRISPR–Cas13d platform for multiplexed transcriptomic regulation and metabolic engineering in primary human T cells. Cell 187, 1278–1295.e20 (2024).
Milcarek, C., Martincic, K., Chung-Ganster, L.-H. & Lutz, C. S. The snRNP-associated U1A levels change following IL-6 stimulation of human B-cells. Mol. Immunol. 39, 809–814 (2003).
Ma, J., Gunderson, S. I. & Phillips, C. Non-snRNP U1A levels decrease during mammalian B-cell differentiation and release the IgM secretory poly(A) site from repression. RNA 12, 122–132 (2006).
So, B. R. et al. A complex of U1 snRNP with cleavage and polyadenylation factors controls telescripting, regulating mRNA transcription in human cells. Mol. Cell 76, 590–599.e4 (2019).
Enders, A. et al. Zinc-finger protein ZFP318 is essential for expression of IgD, the alternatively spliced Igh product made by mature B lymphocytes. Proc. Natl Acad. Sci. USA 111, 4513–4518 (2014).
Pioli, P. D., Debnath, I., Weis, J. J. & Weis, J. H. Zfp318 regulates IgD expression by abrogating transcription termination within the Ighm/Ighd locus. J. Immunol. 193, 2546–2553 (2014).
Wang, Y. et al. High recallability of memory B cells requires ZFP318-dependent transcriptional regulation of mitochondrial function. Immunity 57, 1848–1863.e7 (2024).
Shell, S. A., Martincic, K., Tran, J. & Milcarek, C. Increased phosphorylation of the carboxyl-terminal domain of RNA polymerase II and loading of polyadenylation and cotranscriptional factors contribute to regulation of the ig heavy chain mRNA in plasma cells. J. Immunol. 179, 7663–7673 (2007).
Martincic, K., Alkan, S. A., Cheatle, A., Borghesi, L. & Milcarek, C. Transcription elongation factor ELL2 directs immunoglobulin secretion in plasma cells by stimulating altered RNA processing. Nat. Immunol. 10, 1102–1109 (2009).
Fusby, B. et al. Coordination of RNA polymerase II pausing and 3′ end processing factor recruitment with alternative polyadenylation. Mol. Cell. Biol. 36, 295–303 (2016).
Mason, J. O., Williams, G. T. & Neuberger, M. S. The half-life of immunoglobulin mRNA increases during B-cell differentiation: a possible role for targeting to membrane-bound polysomes. Genes Dev. 2, 1003–1011 (1988).
Herrero, A. B. et al. FAM46C controls antibody production by the polyadenylation of immunoglobulin mRNAs and inhibits cell migration in multiple myeloma. J. Cell. Mol. Med. 24, 4171–4182 (2020).
Manfrini, N. et al. FAM46C and FNDC3A are multiple myeloma tumor suppressors that act in concert to impair clearing of protein aggregates and autophagy. Cancer Res. 80, 4693–4706 (2020).
Fucci, C. et al. The interaction of the tumor suppressor FAM46C with p62 and FNDC3 proteins integrates protein and secretory homeostasis. Cell Rep. 32, 108162 (2020).
Benson, M. J. et al. Heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL) and elongation factor, RNA polymerase II, 2 (ELL2) are regulators of mRNA processing in plasma cells. Proc. Natl Acad. Sci. USA 109, 16252–16257 (2012).
Nelson, A. M., Carew, N. T., Smith, S. M. & Milcarek, C. RNA splicing in the transition from B cells to antibody-secreting cells: the influences of ELL2, small nuclear RNA, and endoplasmic reticulum stress. J. Immunol. 201, 3073–3083 (2018).
Park, K. S. et al. Transcription elongation factor ELL2 drives Ig secretory-specific mRNA production and the unfolded protein response. J. Immunol. 193, 4663–4674 (2014).
Smith, J. & Bartel, D. P. The G3BP stress-granule proteins reinforce the translation program of the integrated stress response. Preprint at bioRxiv https://doi.org/10.1101/2024.10.04.616305 (2024).
Holman, H. & Deicher, H. R. The reaction of the lupus erythematosus (L.E.) cell factor with deoxyribonucleoprotein of the cell nucleus. J. Clin. Investig. 38, 2059–2072 (1959).
Sharp, G. C. et al. Association of antibodies to ribonucleoprotein and Sm antigens with mixed connective-tissue disease, systemic lupus erythematosus and other rheumatic diseases. N. Engl. J. Med. 295, 1149–1154 (1976).
Tan, E. M. & Kunkel, H. G. Characteristics of a soluble nuclear antigen precipitating with sera of patients with systemic lupus erythematosus. J. Immunol. 96, 464–471 (1966).
van Beers, J. J. B. C. & Schreurs, M. W. J. Anti-Sm antibodies in the classification criteria of systemic lupus erythematosus. J. Transl. Autoimmun. 5, 100155 (2022).
White, P. J., Gardner, W. D. & Hoch, S. O. Identification of the immunogenically active components of the Sm and RNP antigens. Proc. Natl Acad. Sci. USA 78, 626–630 (1981).
Battle, D. J. et al. The SMN complex: an assembly machine for RNPs. Cold Spring Harb. Symp. Quant. Biol. 71, 313–320 (2006).
Hassfeld, W. et al. Demonstration of a new antinuclear antibody (anti-RA33) that is highly specific for rheumatoid arthritis. Arthritis Rheum. 32, 1515–1520 (1989).
Eystathioy, T. et al. A phosphorylated cytoplasmic autoantigen, GW182, associates with a unique population of human mRNAs within novel cytoplasmic speckles. Mol. Biol. Cell 13, 1338–1351 (2002).
Braun, J. E., Huntzinger, E. & Izaurralde, E. Ten years of progress in GW/P body research. Adv. Exp. Med. Biol. 768, 147–163 (2012).
Dou, D. R. et al. Xist ribonucleoproteins promote female sex-biased autoimmunity. Cell 187, 733–749.e16 (2024). This study reports functional demonstration of RNP-driven autoimmune disease and rationalization for the female bias of lupus erythematosus.
Levine, T. D., Gao, F., King, P. H., Andrews, L. G. & Keene, J. D. Hel-N1: an autoimmune RNA-binding protein with specificity for 3’ uridylate-rich untranslated regions of growth factor mRNAs. Mol. Cell. Biol. 13, 3494–3504 (1993).
Szabo, A. et al. HuD, a paraneoplastic encephalomyelitis antigen, contains RNA-binding domains and is homologous to Elav and Sex-lethal. Cell 67, 325–333 (1991).
King, P. H. & Dropcho, E. J. Expression of Hel-N1 and HeL-N2 in small-cell lung carcinoma. Ann. Neurol. 39, 679–681 (1996).
Alspaugh, M. A. & Tan, E. M. Antibodies to cellular antigens in Sjögren’s syndrome. J. Clin. Investig. 55, 1067–1073 (1975).
Lerner, M. R., Boyle, J. A., Hardin, J. A. & Steitz, J. A. Two novel classes of small ribonucleoproteins detected by antibodies associated with lupus erythematosus. Science 211, 400–402 (1981).
Wolin, S. L. & Steitz, J. A. The Ro small cytoplasmic ribonucleoproteins: identification of the antigenic protein and its binding site on the Ro RNAs. Proc. Natl Acad. Sci. USA 81, 1996–2000 (1984).
Ben-Chetrit, E., Chan, E. K., Sullivan, K. F. & Tan, E. M. A 52-kD protein is a novel component of the SS-A/Ro antigenic particle. J. Exp. Med. 167, 1560–1571 (1988).
Green, C. D., Long, K. S., Shi, H. & Wolin, S. L. Binding of the 60-kDa Ro autoantigen to Y RNAs: evidence for recognition in the major groove of a conserved helix. RNA 4, 750–765 (1998).
Su, X. et al. The noncoding RNAs SNORD50A and SNORD50B-mediated TRIM21–GMPS interaction promotes the growth of p53 wild-type breast cancers by degrading p53. Cell Death Differ. 28, 2450–2464 (2021).
Ge, Q., Nilasena, D. S., O’Brien, C. A., Frank, M. B. & Targoff, I. N. Molecular analysis of a major antigenic region of the 240-kD protein of Mi-2 autoantigen. J. Clin. Investig. 96, 1730–1737 (1995).
Seelig, H. P. et al. The major dermatomyositis-specific Mi-2 autoantigen is a presumed helicase involved in transcriptional activation. Arthritis Rheum. 38, 1389–1399 (1995).
Zhang, Y., LeRoy, G., Seelig, H.-P., Lane, W. S. & Reinberg, D. The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities. Cell 95, 279–289 (1998).
Mathews, M. B. & Bernstein, R. M. Myositis autoantibody inhibits histidyl-tRNA synthetase: a model for autoimmunity. Nature 304, 177–179 (1983).
Eenennaam, H. V. et al. Identity of the RNase MRP- and RNase P-associated Th/To autoantigen. Arthritis Rheum. 46, 3266–3272 (2002).
Williams, S. G. & Wolin, S. L. The autoantigen repertoire and the microbial RNP world. Trends Mol. Med. 27, 422–435 (2021).
Salomonsson, S. et al. Ro/SSA autoantibodies directly bind cardiomyocytes, disturb calcium homeostasis, and mediate congenital heart block. J. Exp. Med. 201, 11–17 (2005).
Brown, G. J. et al. TLR7 gain-of-function genetic variation causes human lupus. Nature 605, 349–356 (2022). This study links human genetics to previous work, which suggested that the deregulated recognition of RNA within a cell can act as a driving force for immune cell activation and autoimmune disease.
Chu, C. et al. Systematic discovery of Xist RNA binding proteins. Cell 161, 404–416 (2015).
Minajigi, A. et al. A comprehensive Xist interactome reveals cohesin repulsion and an RNA-directed chromosome conformation. Science 349 aab2276 (2015).
Yu, B. et al. B cell-specific XIST complex enforces X-inactivation and restrains atypical B cells. Cell 184, 1790–1803.e17 (2021).
Ha, N. et al. The lupus autoantigen La/Ssb is an Xist-binding protein involved in Xist folding and cloud formation. Nucleic Acids Res. 49, 11596–11613 (2021).
Patil, D. P. et al. m6A RNA methylation promotes XIST-mediated transcriptional repression. Nature 537, 369–373 (2016).
Lovell, C. D., Jiwrajka, N., Amerman, H. K., Cancro, M. P. & Anguera, M. Xist deletion in B cells results in systemic lupus erythematosus phenotypes. Preprint at bioRxiv https://doi.org/10.1101/2024.05.15.594175 (2024).
Boccitto, M. & Wolin, S. L. Ro60 and Y RNAs: structure, functions, and roles in autoimmunity. Crit. Rev. Biochem. Mol. Biol. 54, 133–152 (2019).
Porat, J., Kothe, U. & Bayfield, M. A. Revisiting tRNA chaperones: new players in an ancient game. RNA 27, 543–559 (2021).
Lu, S. X. et al. Pharmacologic modulation of RNA splicing enhances anti-tumor immunity. Cell 184, 4032–4047.e31 (2021).
Darrigrand, R. et al. Isoginkgetin derivative IP2 enhances the adaptive immune response against tumor antigens. Commun. Biol. 4, 269 (2021).
Cortés-López, M. et al. High-throughput mutagenesis identifies mutations and RNA-binding proteins controlling CD19 splicing and CART-19 therapy resistance. Nat. Commun. 13, 5570 (2022).
Ziegler, N. et al. Analysis of RBP expression and binding sites identifies PTBP1 as a regulator of CD19 expression in B-ALL. OncoImmunology 12, 2184143 (2023).
Witkowski, M. T. et al. NUDT21 limits CD19 levels through alternative mRNA polyadenylation in B cell acute lymphoblastic leukemia. Nat. Immunol. 23, 1424–1432 (2022). Leukaemic cells co-opt the cleavage and polyadenylation machinery to downregulate antigen and to evade recognition by CAR-T cells.
Iwai, N. et al. UPF1 plays critical roles in early B cell development. Nat. Commun. 15, 5765 (2024). This study reports a critical role for the RNA helicase UPF1 in VDJ recombination and for B cell differentiation following recombination of the Ig L-chain.
Monaghan, L., Longman, D. & Cáceres, J. F. Translation-coupled mRNA quality control mechanisms. EMBO J. 42, EMBJ2023114378 (2023).
Pastor, F., Kolonias, D., Giangrande, P. H. & Gilboa, E. Induction of tumour immunity by targeted inhibition of nonsense-mediated mRNA decay. Nature 465, 227–230 (2010).
Oka, M. et al. Aberrant splicing isoforms detected by full-length transcriptome sequencing as transcripts of potential neoantigens in non-small cell lung cancer. Genome Biol. 22, 9 (2021).
Becker, J. P. et al. NMD inhibition by 5-azacytidine augments presentation of immunogenic frameshift-derived neoepitopes. iScience 24, 102389 (2021).
Cook, A. L. et al. Identification of nonsense-mediated decay inhibitors that alter the tumor immune landscape. eLife 13, RP95952 (2024).
Kwok, D. W. et al. Tumour-wide RNA splicing aberrations generate actionable public neoantigens. Nature 639, 463–473 (2025). This study rationalizes the utilization and discovery of tumour neoantigens derived from aberrant splicing events, which have therapeutic potential.
Musaev, D. et al. UPF1 regulates mRNA stability by sensing poorly translated coding sequences. Cell Rep. 43, 114074 (2024).
Welte, T. et al. Convergence of multiple RNA-silencing pathways on GW182/TNRC6. Mol. Cell 83, 2478–2492.e8 (2023).
Matsushita, K. et al. Zc3h12a is an RNase essential for controlling immune responses by regulating mRNA decay. Nature 458, 1185–1190 (2009).
Liang, J. et al. MCP-induced protein 1 deubiquitinates TRAF proteins and negatively regulates JNK and NF-kappaB signaling. J. Exp. Med. 207, 2959–2973 (2010).
Wadowska, M. et al. MCP-induced protein 1 participates in macrophage-dependent endotoxin tolerance. J. Immunol. 209, 1348–1358 (2022).
Bhat, N. et al. Regnase-1 is essential for B cell homeostasis to prevent immunopathology. J. Exp. Med. 218, e20200971 (2021).
Nakatsuka, Y. et al. Profibrotic function of pulmonary group 2 innate lymphoid cells is controlled by regnase-1. Eur. Respir. J. 57, 2000018 (2021).
Yaku, A. et al. Regnase-1 prevents pulmonary arterial hypertension through mRNA degradation of interleukin-6 and platelet-derived growth factor in alveolar macrophages. Circulation 146, 1006–1022 (2022).
Uehata, T. et al. Regulation of lymphoid-myeloid lineage bias through regnase-1/3-mediated control of Nfkbiz. Blood 143, 243–257 (2024).
Garg, A. V. et al. MCPIP1 endoribonuclease activity negatively regulates interleukin-17-mediated signaling and inflammation. Immunity 43, 475–487 (2015).
Monin, L. et al. MCPIP1/Regnase-1 restricts IL-17A- and IL-17C-dependent skin inflammation. J. Immunol. 198, 767–775 (2017).
Trevejo-Nuñez, G. et al. Regnase-1 deficiency restrains Klebsiella pneumoniae infection by regulation of a type I interferon response. mBio 13, e03792-21 (2022).
Habacher, C. & Ciosk, R. ZC3H12A/MCPIP1/Regnase-1-related endonucleases: an evolutionary perspective on molecular mechanisms and biological functions. BioEssays 39, 1700051 (2017).
Gamm, M. von et al. Immune homeostasis and regulation of the interferon pathway require myeloid-derived Regnase-3. J. Exp. Med. 216, 1700–1723 (2019).
Bataclan, M. et al. Crosstalk between Regnase-1 and -3 shapes mast cell survival and cytokine expression. Life Sci. Alliance 7, e202402784 (2024). This study provides evidence for cooperative and unique functions of Regnase paralogues in mast cells and for the regulatory interaction between these RBPs.
Cuchet-Lourenço, D. et al. VCAM1-expressing T cells and systemic autoimmunity in Regnase-1 deficiency. Preprint at medRxiv https://doi.org/10.1101/2025.01.21.25320127 (2025).
Sun, X. et al. Deletion of the mRNA endonuclease Regnase-1 promotes NK cell anti-tumor activity via OCT2-dependent transcription of Ifng. Immunity 57, 1360–1377.e13 (2024).
Zheng, W. et al. Regnase-1 suppresses TCF-1+ precursor exhausted T-cell formation to limit CAR-T-cell responses against ALL. Blood 138, 122–135 (2021).
Wang, L. et al. Induction of immortal-like and functional CAR T cells by defined factors. J. Exp. Med. 221, e20232368 (2024).
Iwasaki, H. et al. The IκB kinase complex regulates the stability of cytokine-encoding mRNA induced by TLR-IL-1R by controlling degradation of regnase-1. Nat. Immunol. 12, 1167–1175 (2011).
Tse, K. M. et al. Enhancement of Regnase-1 expression with stem loop-targeting antisense oligonucleotides alleviates inflammatory diseases. Sci. Transl. Med. 14, eabo2137 (2022).
Suzuki, H. I. et al. MCPIP1 ribonuclease antagonizes dicer and terminates microRNA biogenesis through precursor microRNA degradation. Mol. Cell 44, 424–436 (2011).
Xiang, J. S., Schafer, D. M., Rothamel, K. L. & Yeo, G. W. Decoding protein–RNA interactions using CLIP-based methodologies. Nat. Rev. Genet. 25, 879–895 (2024).
Mukherjee, N. et al. Global target mRNA specification and regulation by the RNA-binding protein ZFP36. Genome Biol. 15, R12 (2014).
Wilamowski, M., Gorecki, A., Dziedzicka-Wasylewska, M. & Jura, J. Substrate specificity of human MCPIP1 endoribonuclease. Sci. Rep. 8, 7381 (2018).
Matheson, L. S. et al. Multiomics analysis couples mRNA turnover and translational control of glutamine metabolism to the differentiation of the activated CD4+ T cell. Sci. Rep. 12, 19657 (2022). This study provides evidence for RBPs mediating the post-transcriptional regulation of many mRNAs encoding enzymes of metabolic pathways, which influence the differentiation of cytotoxic CD4 T cells.
Harris, S. E. et al. Understanding species-specific and conserved RNA–protein interactions in vivo and in vitro. Nat. Commun. 15, 8400 (2024).
Capitanchik, C., Wilkins, O. G., Wagner, N., Gagneur, J. & Ule, J. From computational models of the splicing code to regulatory mechanisms and therapeutic implications. Nat. Rev. Genet. 26, 171–190 (2024).
Hwang, H., Jeon, H., Yeo, N. & Baek, D. Big data and deep learning for RNA biology. Exp. Mol. Med. 56, 1293–1321 (2024).