
The RNA-binding E3 ligase MKRN2 selectively disrupts Il6 translation to restrain inflammation
Kawai, T. & Akira, S. TLR signaling. Cell Death Differ. 13, 816–825 (2006).
Medzhitov, R. & Horng, T. Transcriptional control of the inflammatory response. Nat. Rev. Immunol. 9, 692–703 (2009).
Taams, L. S. Inflammation and immune resolution. Clin. Exp. Immunol. 193, 1–2 (2018).
Anderson, P. Post-transcriptional control of cytokine production. Nat. Immunol. 9, 353–359 (2008).
Cao, X. Self-regulation and cross-regulation of pattern-recognition receptor signalling in health and disease. Nat. Rev. Immunol. 16, 35–50 (2016).
Zhang, Q. & Cao, X. Epigenetic remodeling in innate immunity and inflammation. Annu. Rev. Immunol. 39, 279–311 (2021).
Smale, S. T. Transcriptional regulation in the innate immune system. Curr. Opin. Immunol. 24, 51–57 (2012).
Liu, J., Qian, C. & Cao, X. Post-translational modification control of innate immunity. Immunity 45, 15–30 (2016).
Liu, J. & Cao, X. RBP–RNA interactions in the control of autoimmunity and autoinflammation. Cell Res. 33, 97–115 (2023).
Carpenter, S., Ricci, E. P., Mercier, B. C., Moore, M. J. & Fitzgerald, K. A. Post-transcriptional regulation of gene expression in innate immunity. Nat. Rev. Immunol. 14, 361–376 (2014).
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).
Akira, S. & Maeda, K. Control of RNA stability in immunity. Annu. Rev. Immunol. 39, 481–509 (2021).
Zinngrebe, J., Montinaro, A., Peltzer, N. & Walczak, H. Ubiquitin in the immune system. EMBO Rep. 15, 28–45 (2014).
van Gent, M., Sparrer, K. M. J. & Gack, M. U. TRIM proteins and their roles in antiviral host defenses. Annu. Rev. Virol. 5, 385–405 (2018).
Jiang, X. & Chen, Z. J. The role of ubiquitylation in immune defence and pathogen evasion. Nat. Rev. Immunol. 12, 35–48 (2011).
Leppek, K. et al. Roquin promotes constitutive mRNA decay via a conserved class of stem-loop recognition motifs. Cell 53, 869–881 (2013).
Kuniyoshi, K. et al. Pivotal role of RNA-binding E3 ubiquitin ligase MEX3C in RIG-I-mediated antiviral innate immunity. Proc. Natl Acad. Sci. USA 111, 5646–5651 (2014).
Jackson, R. J., Hellen, C. U. & Pestova, T. V. The mechanism of eukaryotic translation initiation and principles of its regulation. Nat. Rev. Mol. Cell Biol. 11, 113–127 (2010).
Wells, S. E., Hillner, P. E., Vale, R. D. & Sachs, A. B. Circularization of mRNA by eukaryotic translation initiation factors. Mol. Cell. 2, 135–140 (1998).
Imataka, H., Gradi, A. & Sonenberg, N. A newly identified N-terminal amino acid sequence of human eIF4G binds poly(A)-binding protein and functions in poly(A)-dependent translation. EMBO J. 17, 7480–7489 (1998).
Craig, A. W., Haghighat, A., Yu, A. T. & Sonenberg, N. Interaction of poly(A)denylate-binding protein with the eIF4G homologue PAIP enhances translation. Nature 392, 520–523 (1998).
Martineau, Y. et al. Poly(A)-binding protein-interacting protein 1 binds to eukaryotic translation initiation factor 3 to stimulate translation. Mol. Cell. Biol. 28, 6658–6667 (2008).
Ahmad, S. Unlocking TH17-cell differentiation. Nat. Rev. Immunol. 6, 793 (2006).
Neurath, M. F. Cytokines in inflammatory bowel disease. Nat. Rev. Immunol. 14, 329–342 (2014).
Kawai, T. & Akira, S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat. Immunol. 11, 373–384 (2010).
Shin, C. et al. MKRN2 is a novel ubiquitin E3 ligase for the p65 subunit of NF-κB and negatively regulates inflammatory responses. Sci. Rep. 7, 46097 (2017).
Niepmann, M. & Gerresheim, G. K. Hepatitis C virus translation regulation. Int. J. Mol. Sci. 21, 2328 (2020).
Dominski, Z. & Marzluff, W. F. Formation of the 3′ end of histone mRNA: getting closer to the end. Gene 396, 373–390 (2007).
Bilinski, C., Burleson, J. & Forouhar, F. Inflammation associated with neoplastic colonic polyps. Ann. Clin. Lab. Sci. 42, 266–270 (2012).
Zhang, Q. & Cao, X. Epigenetic regulation of the innate immune response to infection. Nat. Rev. Immunol. 19, 417–432 (2019).
Hunter, C. & Jones, S. IL-6 as a keystone cytokine in health and disease. Nat. Immunol. 16, 448–457 (2015).
Mosteiro, L., Pantoja, C., de Martino, A. & Serrano, M. Senescence promotes in vivo reprogramming through p16INK4a and IL-6. Aging Cell 17, e12711 (2018).
Hao, X. et al. TXNRD1 drives the innate immune response in senescent cells with implications for age-associated inflammation. Nat. Aging 4, 185–197 (2024).
Warde, K. M. et al. Senescence-induced immune remodeling facilitates metastatic adrenal cancer in a sex-dimorphic manner. Nat. Aging 3, 846–865 (2023).
Choe, J. et al. mRNA circularization by METTL3–eIF3h enhances translation and promotes oncogenesis. Nature 561, 556–560 (2018).
Roy, G. et al. PAIP1 interacts with poly(A) binding protein through two independent binding motifs. Mol. Cell. Biol. 22, 3769–3782 (2022).
Beck, D. B., Werner, A., Kastner, D. L. & Aksentijevich, I. Disorders of ubiquitylation: unchained inflammation. Nat. Rev. Rheumatol. 18, 435–447 (2022).
Wang, L. et al. MKRN2 knockout causes male infertility through decreasing STAT1, SIX4, and TNC expression. Front. Endocrinol. 14, 1138096 (2023).
Liu, Z. et al. MKRN2 inhibits the proliferation of gastric cancer by downregulating PKM2. Aging 14, 2004–2013 (2022).
Zhang, Y., Cui, N. & Zheng, G. Ubiquitination of P53 by E3 ligase MKRN2 promotes melanoma cell proliferation. Oncol. Lett. 19, 1975–1984 (2020).
Yang, P. H. et al. Makorin-2 is a neurogenesis inhibitor downstream of phosphatidylinositol 3-kinase/AKT (PI3K/AKT) signal. J. Biol. Chem. 283, 8486–8495 (2008).
Cheung, W. K. et al. Identification of protein domains required for makorin-2-mediated neurogenesis inhibition in Xenopus embryos. Biochem. Biophys. Res. Commun. 394, 18–23 (2010).
Wolf, E. J. et al. MKRN2 physically interacts with GLE1 to regulate mRNA export and zebrafish retinal development. Cell Rep. 31, 107693 (2020).
Zhao, W., Liu, M. & Kirkwood, K. L. p38a stabilizes interleukin-6 mRNA via multiple AU-rich elements. J. Biol. Chem. 283, 1778–1785 (2008).
Paschoud, S. et al. Destabilization of interleukin-6 mRNA requires a putative RNA stem-loop structure, an AU-rich element, and the RNA-binding protein AUF1. Mol. Cell. Biol. 26, 8228–8241 (2006).
Yang, M. et al. K33-linked polyubiquitination of Zap70 by Nrdp1 controls CD8+ T cell activation. Nat. Immunol. 16, 1253–1262 (2015).
Zhang, Q. et al. Tet2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6. Nature 525, 389–393 (2015).
Yu, Z. et al. Lys29-linkage of ASK1 by Skp1–Cullin 1–Fbxo21 ubiquitin ligase complex is required for antiviral innate response. eLife 5, e14087 (2016).
Blue, S. M. et al. Transcriptome-wide identification of RNA-binding protein binding sites using seCLIP–seq. Nat. Protoc. 17, 1223–1265 (2022).
Lu, D. et al. The phosphatase DUSP2 controls the activity of the transcription activator STAT3 and regulates TH17 differentiation. Nat. Immunol. 16, 1263–1273 (2015).
Zhao, R. et al. Nucleophosmin 1 promotes mucosal immunity by supporting mitochondrial oxidative phosphorylation and ILC3 activity. Nat. Immunol. 25, 1565–1579 (2024).