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Abstract

Posttranscriptional control of mRNA regulates various biological processes, including inflammatory and immune responses. RNA-binding proteins (RBPs) bind regulatory elements in the 3′ untranslated regions (UTRs) of mRNA and regulate mRNA turnover and translation. In particular, eight RBPs (TTP, AUF1, KSRP, TIA-1/TIAR, Roquin, Regnase, HuR, and Arid5a) have been extensively studied and are key posttranscriptional regulators of inflammation and immune responses. These RBPs sometimes collaboratively or competitively bind the same target mRNA to enhance or dampen regulatory activities. These RBPs can also bind their own 3′ UTRs to negatively or positively regulate their expression. Both upstream signaling pathways and microRNA regulation shape the interactions between RBPs and target RNA. Dysregulation of RBPs results in chronic inflammation and autoimmunity. Here, we summarize the functional roles of these eight RBPs in immunity and their associated diseases.

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2021-04-26
2024-05-03
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Literature Cited

  1. 1. 
    Medzhitov R. 2007. Recognition of microorganisms and activation of the immune response. Nature 449:819–26
    [Google Scholar]
  2. 2. 
    Kawai T, Akira S. 2009. The roles of TLRs, RLRs and NLRs in pathogen recognition. Int. Immunol. 21:317–37
    [Google Scholar]
  3. 3. 
    Anderson P. 2010. Post-transcriptional regulons coordinate the initiation and resolution of inflammation. Nat. Rev. Immunol. 10:24–35
    [Google Scholar]
  4. 4. 
    Bartel DP. 2018. Metazoan microRNAs. Cell 173:20–51
    [Google Scholar]
  5. 5. 
    Ambros V, Ruvkun G 2018. Recent molecular genetic explorations of Caenorhabditis elegans microRNAs. Genetics 209:651–73
    [Google Scholar]
  6. 6. 
    Treiber T, Treiber N, Meister G. 2019. Regulation of microRNA biogenesis and its crosstalk with other cellular pathways. Nat. Rev. Mol. Cell Biol. 20:5–20
    [Google Scholar]
  7. 7. 
    Chen YG, Satpathy AT, Chang HY. 2017. Gene regulation in the immune system by long noncoding RNAs. Nat. Immunol. 18:962–72
    [Google Scholar]
  8. 8. 
    Necsulea A, Kaessmann H. 2014. Evolutionary dynamics of coding and non-coding transcriptomes. Nat. Rev. Genet. 15:734–48
    [Google Scholar]
  9. 9. 
    Cabili MN, Trapnell C, Goff L, Koziol M, Tazon-Vega B et al. 2011. Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev. 25:1915–27
    [Google Scholar]
  10. 10. 
    Hezroni H, Koppstein D, Schwartz MG, Avrutin A, Bartel DP, Ulitsky I. 2015. Principles of long noncoding RNA evolution derived from direct comparison of transcriptomes in 17 species. Cell Rep. 11:1110–22
    [Google Scholar]
  11. 11. 
    Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S et al. 2012. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res. 22:1775–89
    [Google Scholar]
  12. 12. 
    Rashid F, Shah A, Shan G. 2016. Long non-coding RNAs in the cytoplasm. Genomics Proteom. Bioinform. 14:73–80
    [Google Scholar]
  13. 13. 
    Ulitsky I, Shkumatava A, Jan CH, Sive H, Bartel DP. 2011. Conserved function of lincRNAs in vertebrate embryonic development despite rapid sequence evolution. Cell 147:1537–50
    [Google Scholar]
  14. 14. 
    Rinn JL, Chang HY. 2012. Genome regulation by long noncoding RNAs. Annu. Rev. Biochem. 81:145–66
    [Google Scholar]
  15. 15. 
    Atianand MK, Caffrey DR, Fitzgerald KA. 2017. Immunobiology of long noncoding RNAs. Annu. Rev. Immunol. 35:177–98
    [Google Scholar]
  16. 16. 
    Jackson R, Kroehling L, Khitun A, Bailis W, Jarret A et al. 2018. The translation of non-canonical open reading frames controls mucosal immunity. Nature 564:434–38
    [Google Scholar]
  17. 17. 
    Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J et al. 2013. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495:333–38
    [Google Scholar]
  18. 18. 
    Chen LL, Yang L 2015. Regulation of circRNA biogenesis. RNA Biol 12:381–88
    [Google Scholar]
  19. 19. 
    Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B et al. 2013. Natural RNA circles function as efficient microRNA sponges. Nature 495:384–88
    [Google Scholar]
  20. 20. 
    Pamudurti NR, Bartok O, Jens M, Ashwal-Fluss R, Stottmeister C et al. 2017. Translation of circRNAs. Mol. Cell 66:9–21.e7
    [Google Scholar]
  21. 21. 
    Natoli G, Andrau JC. 2012. Noncoding transcription at enhancers: general principles and functional models. Annu. Rev. Genet. 46:1–19
    [Google Scholar]
  22. 22. 
    Andersson R, Gebhard C, Miguel-Escalada I, Hoof I, Bornholdt J et al. 2014. An atlas of active enhancers across human cell types and tissues. Nature 507:455–61
    [Google Scholar]
  23. 23. 
    Sartorelli V, Lauberth SM. 2020. Enhancer RNAs are an important regulatory layer of the epigenome. Nat. Struct. Mol. Biol. 27:521–28
    [Google Scholar]
  24. 24. 
    Desrosiers R, Friderici K, Rottman F 1974. Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells. PNAS 71:3971–75
    [Google Scholar]
  25. 25. 
    Xiao S, Cao S, Huang Q, Xia L, Deng M et al. 2019. The RNA N6-methyladenosine modification landscape of human fetal tissues. Nat. Cell Biol. 21:651–61
    [Google Scholar]
  26. 26. 
    Jia G, Fu Y, Zhao X, Dai Q, Zheng G et al. 2011. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat. Chem. Biol. 7:885–87
    [Google Scholar]
  27. 27. 
    Zhao BS, Roundtree IA, He C. 2017. Post-transcriptional gene regulation by mRNA modifications. Nat. Rev. Mol. Cell Biol. 18:31–42
    [Google Scholar]
  28. 28. 
    Meyer KD, Jaffrey SR. 2017. Rethinking m6A readers, writers, and erasers. Annu. Rev. Cell Dev. Biol. 33:319–42
    [Google Scholar]
  29. 29. 
    Zhou J, Wan J, Gao X, Zhang X, Jaffrey SR, Qian SB. 2015. Dynamic m6A mRNA methylation directs translational control of heat shock response. Nature 526:591–94
    [Google Scholar]
  30. 30. 
    Xiang Y, Laurent B, Hsu CH, Nachtergaele S, Lu Z et al. 2017. RNA m6A methylation regulates the ultraviolet-induced DNA damage response. Nature 543:573–76
    [Google Scholar]
  31. 31. 
    Ries RJ, Zaccara S, Klein P, Olarerin-George A, Namkoong S et al. 2019. m6A enhances the phase separation potential of mRNA. Nature 571:424–28
    [Google Scholar]
  32. 32. 
    Gao Y, Pei G, Li D, Li R, Shao Y et al. 2019. Multivalent m6A motifs promote phase separation of YTHDF proteins. Cell Res. 29:767–69
    [Google Scholar]
  33. 33. 
    Sanduja S, Blanco FF, Young LE, Kaza V, Dixon DA. 2012. The role of tristetraprolin in cancer and inflammation. Front. Biosci. 17:174–88
    [Google Scholar]
  34. 34. 
    Patial S, Blackshear PJ. 2016. Tristetraprolin as a therapeutic target in inflammatory disease. Trends Pharmacol. Sci. 37:811–21
    [Google Scholar]
  35. 35. 
    Clark AR, Dean JL. 2016. The control of inflammation via the phosphorylation and dephosphorylation of tristetraprolin: a tale of two phosphatases. Biochem. Soc. Trans. 44:1321–37
    [Google Scholar]
  36. 36. 
    Stoecklin G, Stubbs T, Kedersha N, Wax S, Rigby WF et al. 2004. MK2-induced tristetraprolin:14-3-3 complexes prevent stress granule association and ARE-mRNA decay. EMBO J 23:1313–24
    [Google Scholar]
  37. 37. 
    Marchese FP, Aubareda A, Tudor C, Saklatvala J, Clark AR, Dean JL. 2010. MAPKAP kinase 2 blocks tristetraprolin-directed mRNA decay by inhibiting CAF1 deadenylase recruitment. J. Biol. Chem. 285:27590–600
    [Google Scholar]
  38. 38. 
    Sun L, Stoecklin G, Van Way S, Hinkovska-Galcheva V, Guo RF et al. 2007. Tristetraprolin (TTP)-14-3-3 complex formation protects TTP from dephosphorylation by protein phosphatase 2a and stabilizes tumor necrosis factor-α mRNA. J. Biol. Chem. 282:3766–77
    [Google Scholar]
  39. 39. 
    Liang J, Lei T, Song Y, Yanes N, Qi Y, Fu M. 2009. RNA-destabilizing factor tristetraprolin negatively regulates NF-κB signaling. J. Biol. Chem. 284:29383–90
    [Google Scholar]
  40. 40. 
    Schichl YM, Resch U, Hofer-Warbinek R, de Martin R. 2009. Tristetraprolin impairs NF-κB/p65 nuclear translocation. J. Biol. Chem. 284:29571–81
    [Google Scholar]
  41. 41. 
    Wagner BJ, DeMaria CT, Sun Y, Wilson GM, Brewer G. 1998. Structure and genomic organization of the human AUF1 gene: alternative pre-mRNA splicing generates four protein isoforms. Genomics 48:195–202
    [Google Scholar]
  42. 42. 
    Zucconi BE, Wilson GM. 2011. Modulation of neoplastic gene regulatory pathways by the RNA-binding factor AUF1. Front. Biosci. 16:2307–25
    [Google Scholar]
  43. 43. 
    White EJ, Brewer G, Wilson GM. 2013. Post-transcriptional control of gene expression by AUF1: mechanisms, physiological targets, and regulation. Biochim. Biophys. Acta Gene Regul. Mech. 1829:680–88
    [Google Scholar]
  44. 44. 
    White EJ, Matsangos AE, Wilson GM. 2017. AUF1 regulation of coding and noncoding RNA. Wiley Interdiscip. Rev. RNA 8: https://doi.org/10.1002/wrna.1393
    [Crossref] [Google Scholar]
  45. 45. 
    Briata P, Chen CY, Ramos A, Gherzi R. 2013. Functional and molecular insights into KSRP function in mRNA decay. Biochim. Biophys. Acta Gene Regul. Mech. 1829:689–94
    [Google Scholar]
  46. 46. 
    Briata P, Bordo D, Puppo M, Gorlero F, Rossi M et al. 2016. Diverse roles of the nucleic acid-binding protein KHSRP in cell differentiation and disease. Wiley Interdiscip. Rev. RNA 7:227–40
    [Google Scholar]
  47. 47. 
    Waris S, Wilce MC, Wilce JA. 2014. RNA recognition and stress granule formation by TIA proteins. Int. J. Mol. Sci. 15:23377–88
    [Google Scholar]
  48. 48. 
    Gilks N, Kedersha N, Ayodele M, Shen L, Stoecklin G et al. 2004. Stress granule assembly is mediated by prion-like aggregation of TIA-1. Mol. Biol. Cell 15:5383–98
    [Google Scholar]
  49. 49. 
    Kai M. 2016. Roles of RNA-binding proteins in DNA damage response. Int. J. Mol. Sci. 17:310 Erratum. 2016. Int. J. Mol. Sci. 17:604
    [Google Scholar]
  50. 50. 
    Vinuesa CG, Cook MC, Angelucci C, Athanasopoulos V, Rui L et al. 2005. A RING-type ubiquitin ligase family member required to repress follicular helper T cells and autoimmunity. Nature 435:452–58
    [Google Scholar]
  51. 51. 
    Athanasopoulos V, Ramiscal RR, Vinuesa CG. 2016. ROQUIN signalling pathways in innate and adaptive immunity. Eur. J. Immunol. 46:1082–90
    [Google Scholar]
  52. 52. 
    Baumjohann D, Heissmeyer V. 2018. Posttranscriptional gene regulation of T follicular helper cells by RNA-binding proteins and microRNAs. Front. Immunol. 9:1794
    [Google Scholar]
  53. 53. 
    Leppek K, Schott J, Reitter S, Poetz F, Hammond MC, Stoecklin G. 2013. Roquin promotes constitutive mRNA decay via a conserved class of stem-loop recognition motifs. Cell 153:869–81
    [Google Scholar]
  54. 54. 
    Janowski R, Heinz GA, Schlundt A, Wommelsdorf N, Brenner S et al. 2016. Roquin recognizes a non-canonical hexaloop structure in the 3′-UTR of Ox40. Nat. Commun. 7:11032
    [Google Scholar]
  55. 55. 
    Rehage N, Davydova E, Conrad C, Behrens G, Maiser A et al. 2018. Binding of NUFIP2 to Roquin promotes recognition and regulation of ICOS mRNA. Nat. Commun. 9:299
    [Google Scholar]
  56. 56. 
    Athanasopoulos V, Barker A, Yu D, Tan AH, Srivastava M et al. 2010. The ROQUIN family of proteins localizes to stress granules via the ROQ domain and binds target mRNAs. FEBS J 277:2109–27
    [Google Scholar]
  57. 57. 
    Zhang Q, Fan L, Hou F, Dong A, Wang YX, Tong Y. 2015. New insights into the RNA-binding and E3 ubiquitin ligase activities of Roquins. Sci. Rep. 5:15660
    [Google Scholar]
  58. 58. 
    Maeda K, Akira S. 2017. Regulation of mRNA stability by CCCH-type zinc-finger proteins in immune cells. Int. Immunol. 29:149–55
    [Google Scholar]
  59. 59. 
    Fu M, Blackshear PJ. 2017. RNA-binding proteins in immune regulation: a focus on CCCH zinc finger proteins. Nat. Rev. Immunol. 17:130–43
    [Google Scholar]
  60. 60. 
    Miekus K, Kotlinowski J, Lichawska-Cieslar A, Rys J, Jura J. 2019. Activity of MCPIP1 RNase in tumor associated processes. J. Exp. Clin. Cancer Res. 38:421
    [Google Scholar]
  61. 61. 
    Matsushita K, Takeuchi O, Standley DM, Kumagai Y, Kawagoe T et al. 2009. Zc3h12a is an RNase essential for controlling immune responses by regulating mRNA decay. Nature 458:1185–90
    [Google Scholar]
  62. 62. 
    Iwasaki H, Takeuchi O, Teraguchi S, Matsushita K, Uehata T et al. 2011. The IκB kinase complex regulates the stability of cytokine-encoding mRNA induced by TLR-IL-1R by controlling degradation of regnase-1. Nat. Immunol. 12:1167–75
    [Google Scholar]
  63. 63. 
    Yokogawa M, Tsushima T, Noda NN, Kumeta H, Enokizono Y et al. 2016. Structural basis for the regulation of enzymatic activity of Regnase-1 by domain-domain interactions. Sci. Rep. 6:22324
    [Google Scholar]
  64. 64. 
    Tanaka H, Arima Y, Kamimura D, Tanaka Y, Takahashi N et al. 2019. Phosphorylation-dependent Regnase-1 release from endoplasmic reticulum is critical in IL-17 response. J. Exp. Med. 216:1431–49
    [Google Scholar]
  65. 65. 
    Mino T, Murakawa Y, Fukao A, Vandenbon A, Wessels HH et al. 2015. Regnase-1 and Roquin regulate a common element in inflammatory mRNAs by spatiotemporally distinct mechanisms. Cell 161:1058–73
    [Google Scholar]
  66. 66. 
    Liang J, Saad Y, Lei T, Wang J, Qi D et al. 2010. MCP-induced protein 1 deubiquitinates TRAF proteins and negatively regulates JNK and NF-κB signaling. J. Exp. Med. 207:2959–73
    [Google Scholar]
  67. 67. 
    Wang W, Huang X, Xin HB, Fu M, Xue A, Wu ZH. 2015. TRAF family member-associated NF-κB activator (TANK) inhibits genotoxic nuclear factor κB activation by facilitating deubiquitinase USP10-dependent deubiquitination of TRAF6 ligase. J. Biol. Chem. 290:13372–85
    [Google Scholar]
  68. 68. 
    Srikantan S, Gorospe M. 2012. HuR function in disease. Front. Biosci. 17:189–205
    [Google Scholar]
  69. 69. 
    Yi J, Chang N, Liu X, Guo G, Xue L et al. 2010. Reduced nuclear export of HuR mRNA by HuR is linked to the loss of HuR in replicative senescence. Nucleic Acids Res 38:1547–58
    [Google Scholar]
  70. 70. 
    Dai W, Zhang G, Makeyev EV. 2012. RNA-binding protein HuR autoregulates its expression by promoting alternative polyadenylation site usage. Nucleic Acids Res 40:787–800
    [Google Scholar]
  71. 71. 
    Kullmann M, Gopfert U, Siewe B, Hengst L. 2002. ELAV/Hu proteins inhibit p27 translation via an IRES element in the p27 5′UTR. Genes Dev 16:3087–99
    [Google Scholar]
  72. 72. 
    Grammatikakis I, Abdelmohsen K, Gorospe M. 2017. Posttranslational control of HuR function. Wiley Interdiscip. Rev. RNA 8: https://doi.org/10.1002/wrna.1372
    [Crossref] [Google Scholar]
  73. 73. 
    Masuda K, Ripley B, Nishimura R, Mino T, Takeuchi O et al. 2013. Arid5a controls IL-6 mRNA stability, which contributes to elevation of IL-6 level in vivo. PNAS 110:9409–14
    [Google Scholar]
  74. 74. 
    Nyati KK, Zaman MM, Sharma P, Kishimoto T. 2020. Arid5a, an RNA-binding protein in immune regulation: RNA stability, inflammation, and autoimmunity. Trends Immunol 41:255–68
    [Google Scholar]
  75. 75. 
    Higa M, Oka M, Fujihara Y, Masuda K, Yoneda Y, Kishimoto T 2018. Regulation of inflammatory responses by dynamic subcellular localization of RNA-binding protein Arid5a. PNAS 115:E1214–20
    [Google Scholar]
  76. 76. 
    Metwally H, Tanaka T, Li S, Parajuli G, Kang S et al. 2020. Noncanonical STAT1 phosphorylation expands its transcriptional activity into promoting LPS-induced IL-6 and IL-12p40 production. Sci. Signal. 13:624eaay0574
    [Google Scholar]
  77. 77. 
    Chang N, Yi J, Guo G, Liu X, Shang Y et al. 2010. HuR uses AUF1 as a cofactor to promote p16INK4 mRNA decay. Mol. Cell. Biol. 30:3875–86
    [Google Scholar]
  78. 78. 
    Winzen R, Thakur BK, Dittrich-Breiholz O, Shah M, Redich N et al. 2007. Functional analysis of KSRP interaction with the AU-rich element of interleukin-8 and identification of inflammatory mRNA targets. Mol. Cell. Biol. 27:8388–400
    [Google Scholar]
  79. 79. 
    Poganik JR, Long MJC, Disare MT, Liu X, Chang SH et al. 2019. Post-transcriptional regulation of Nrf2-mRNA by the mRNA-binding proteins HuR and AUF1. FASEB J 33:14636–52
    [Google Scholar]
  80. 80. 
    Linker K, Pautz A, Fechir M, Hubrich T, Greeve J, Kleinert H. 2005. Involvement of KSRP in the post-transcriptional regulation of human iNOS expression—complex interplay of KSRP with TTP and HuR. Nucleic Acids Res 33:4813–27
    [Google Scholar]
  81. 81. 
    Fialcowitz EJ, Brewer BY, Keenan BP, Wilson GM. 2005. A hairpin-like structure within an AU-rich mRNA-destabilizing element regulates trans-factor binding selectivity and mRNA decay kinetics. J. Biol. Chem. 280:22406–17
    [Google Scholar]
  82. 82. 
    Al-Ahmadi W, Al-Ghamdi M, Al-Haj L, Al-Saif M, Khabar KS 2009. Alternative polyadenylation variants of the RNA binding protein, HuR: abundance, role of AU-rich elements and auto-regulation. Nucleic Acids Res 37:3612–24
    [Google Scholar]
  83. 83. 
    Kawai T, Lal A, Yang X, Galban S, Mazan-Mamczarz K, Gorospe M. 2006. Translational control of cytochrome c by RNA-binding proteins TIA-1 and HuR. Mol. Cell. Biol. 26:3295–307
    [Google Scholar]
  84. 84. 
    Zhu H, Hasman RA, Barron VA, Luo G, Lou H. 2006. A nuclear function of Hu proteins as neuron-specific alternative RNA processing regulators. Mol. Biol. Cell 17:5105–14
    [Google Scholar]
  85. 85. 
    Izquierdo JM. 2008. Hu antigen R (HuR) functions as an alternative pre-mRNA splicing regulator of Fas apoptosis-promoting receptor on exon definition. J. Biol. Chem. 283:19077–84
    [Google Scholar]
  86. 86. 
    Kim HH, Kuwano Y, Srikantan S, Lee EK, Martindale JL, Gorospe M. 2009. HuR recruits let-7/RISC to repress c-Myc expression. Genes Dev 23:1743–48
    [Google Scholar]
  87. 87. 
    Trabucchi M, Briata P, Garcia-Mayoral M, Haase AD, Filipowicz W et al. 2009. The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs. Nature 459:1010–14
    [Google Scholar]
  88. 88. 
    Wu X, Chesoni S, Rondeau G, Tempesta C, Patel R et al. 2013. Combinatorial mRNA binding by AUF1 and Argonaute 2 controls decay of selected target mRNAs. Nucleic Acids Res 41:2644–58
    [Google Scholar]
  89. 89. 
    Abdelmohsen K, Tominaga-Yamanaka K, Srikantan S, Yoon JH, Kang MJ, Gorospe M. 2012. RNA-binding protein AUF1 represses Dicer expression. Nucleic Acids Res 40:11531–44
    [Google Scholar]
  90. 90. 
    Srivastava M, Duan G, Kershaw NJ, Athanasopoulos V, Yeo JH et al. 2015. Roquin binds microRNA-146a and Argonaute2 to regulate microRNA homeostasis. Nat. Commun. 6:6253
    [Google Scholar]
  91. 91. 
    Suzuki HI, Arase M, Matsuyama H, Choi YL, Ueno T et al. 2011. MCPIP1 ribonuclease antagonizes dicer and terminates microRNA biogenesis through precursor microRNA degradation. Mol. Cell 44:424–36
    [Google Scholar]
  92. 92. 
    Jonas K, Calin GA, Pichler M. 2020. RNA-binding proteins as important regulators of long non-coding RNAs in cancer. Int. J. Mol. Sci. 21:82969
    [Google Scholar]
  93. 93. 
    Noh JH, Kim KM, Abdelmohsen K, Yoon JH, Panda AC et al. 2016. HuR and GRSF1 modulate the nuclear export and mitochondrial localization of the lncRNA RMRP. Genes Dev 30:1224–39
    [Google Scholar]
  94. 94. 
    Wang Y, Li Y, Toth JI, Petroski MD, Zhang Z, Zhao JC. 2014. N6-Methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nat. Cell Biol. 16:191–98
    [Google Scholar]
  95. 95. 
    Taylor GA, Carballo E, Lee DM, Lai WS, Thompson MJ et al. 1996. A pathogenetic role for TNFα in the syndrome of cachexia, arthritis, and autoimmunity resulting from tristetraprolin (TTP) deficiency. Immunity 4:445–54
    [Google Scholar]
  96. 96. 
    Carballo E, Blackshear PJ. 2001. Roles of tumor necrosis factor-α receptor subtypes in the pathogenesis of the tristetraprolin-deficiency syndrome. Blood 98:2389–95
    [Google Scholar]
  97. 97. 
    Qiu LQ, Stumpo DJ, Blackshear PJ. 2012. Myeloid-specific tristetraprolin deficiency in mice results in extreme lipopolysaccharide sensitivity in an otherwise minimal phenotype. J. Immunol. 188:5150–59
    [Google Scholar]
  98. 98. 
    Haneklaus M, O'Neil JD, Clark AR, Masters SL, O'Neill LAJ 2017. The RNA-binding protein Tristetraprolin (TTP) is a critical negative regulator of the NLRP3 inflammasome. J. Biol. Chem. 292:6869–81
    [Google Scholar]
  99. 99. 
    Ross EA, Smallie T, Ding Q, O'Neil JD, Cunliffe HE et al. 2015. Dominant suppression of inflammation via targeted mutation of the mRNA destabilizing protein tristetraprolin. J. Immunol. 195:265–76
    [Google Scholar]
  100. 100. 
    Lu JY, Sadri N, Schneider RJ. 2006. Endotoxic shock in AUF1 knockout mice mediated by failure to degrade proinflammatory cytokine mRNAs. Genes Dev 20:3174–84
    [Google Scholar]
  101. 101. 
    Zhai B, Yang H, Mancini A, He Q, Antoniou J, Di Battista JA. 2010. Leukotriene B4 BLT receptor signaling regulates the level and stability of cyclooxygenase-2 (COX-2) mRNA through restricted activation of Ras/Raf/ERK/p42 AUF1 pathway. J. Biol. Chem. 285:23568–80
    [Google Scholar]
  102. 102. 
    Sarkar S, Han J, Sinsimer KS, Liao B, Foster RL et al. 2011. RNA-binding protein AUF1 regulates lipopolysaccharide-induced IL10 expression by activating IκB kinase complex in monocytes. Mol. Cell. Biol. 31:602–15
    [Google Scholar]
  103. 103. 
    Ishii T, Hayakawa H, Sekiguchi T, Adachi N, Sekiguchi M. 2015. Role of Auf1 in elimination of oxidatively damaged messenger RNA in human cells. Free Radic. . Biol. Med. 79:109–16
    [Google Scholar]
  104. 104. 
    Zhao H, Wang X, Yi P, Si Y, Tan P et al. 2017. KSRP specifies monocytic and granulocytic differentiation through regulating miR-129 biogenesis and RUNX1 expression. Nat. Commun. 8:1428
    [Google Scholar]
  105. 105. 
    Piecyk M, Wax S, Beck AR, Kedersha N, Gupta M et al. 2000. TIA-1 is a translational silencer that selectively regulates the expression of TNF-α. EMBO J 19:4154–63
    [Google Scholar]
  106. 106. 
    Phillips K, Kedersha N, Shen L, Blackshear PJ, Anderson P 2004. Arthritis suppressor genes TIA-1 and TTP dampen the expression of tumor necrosis factor α, cyclooxygenase 2, and inflammatory arthritis. PNAS 101:2011–16
    [Google Scholar]
  107. 107. 
    Zheng L, Ling W, Zhu D, Li Z, Kong L. 2020. Roquin-1 regulates macrophage immune response and participates in hepatic ischemia-reperfusion injury. J. Immunol. 204:1322–33
    [Google Scholar]
  108. 108. 
    Murakawa Y, Hinz M, Mothes J, Schuetz A, Uhl M et al. 2015. RC3H1 post-transcriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-κB pathway. Nat. Commun. 6:7367
    [Google Scholar]
  109. 109. 
    Maruyama T, Araki T, Kawarazaki Y, Naguro I, Heynen S et al. 2014. Roquin-2 promotes ubiquitin-mediated degradation of ASK1 to regulate stress responses. Sci. Signal. 7:ra8
    [Google Scholar]
  110. 110. 
    Tavernier SJ, Athanasopoulos V, Verloo P, Behrens G, Staal J et al. 2019. A human immune dysregulation syndrome characterized by severe hyperinflammation with a homozygous nonsense Roquin-1 mutation. Nat. Commun. 10:4779
    [Google Scholar]
  111. 111. 
    Sun P, Lu YX, Cheng D, Zhang K, Zheng J et al. 2018. Monocyte chemoattractant protein-induced protein 1 targets hypoxia-inducible factor 1α to protect against hepatic ischemia/reperfusion injury. Hepatology 68:2359–75
    [Google Scholar]
  112. 112. 
    Jin Z, Liang J, Wang J, Kolattukudy PE 2015. MCP-induced protein 1 mediates the minocycline-induced neuroprotection against cerebral ischemia/reperfusion injury in vitro and in vivo. J. Neuro-inflamm. 12:39
    [Google Scholar]
  113. 113. 
    Kapoor N, Niu J, Saad Y, Kumar S, Sirakova T et al. 2015. Transcription factors STAT6 and KLF4 implement macrophage polarization via the dual catalytic powers of MCPIP. J. Immunol. 194:6011–23
    [Google Scholar]
  114. 114. 
    Huang S, Qi D, Liang J, Miao R, Minagawa K et al. 2012. The putative tumor suppressor Zc3h12d modulates toll-like receptor signaling in macrophages. Cell Signal 24:569–76
    [Google Scholar]
  115. 115. 
    Schultz CW, Preet R, Dhir T, Dixon DA, Brody JR. 2020. Understanding and targeting the disease-related RNA binding protein human antigen R (HuR). Wiley Interdiscip. Rev. RNA 11:e1581
    [Google Scholar]
  116. 116. 
    Katsanou V, Papadaki O, Milatos S, Blackshear PJ, Anderson P et al. 2005. HuR as a negative posttranscriptional modulator in inflammation. Mol. Cell 19:777–89
    [Google Scholar]
  117. 117. 
    Dubey PK, Masuda K, Nyati KK, Uz Zaman MM, Chalise JP et al. 2017. Arid5a-deficient mice are highly resistant to bleomycin-induced lung injury. Int. Immunol. 29:79–85
    [Google Scholar]
  118. 118. 
    Nair PM, Starkey MR, Haw TJ, Liu G, Collison AM et al. 2019. Enhancing tristetraprolin activity reduces the severity of cigarette smoke-induced experimental chronic obstructive pulmonary disease. Clin. Transl. Immunol. 8:e01084
    [Google Scholar]
  119. 119. 
    Galloway A, Saveliev A, Lukasiak S, Hodson DJ, Bolland D et al. 2016. RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence. Science 352:453–59
    [Google Scholar]
  120. 120. 
    Nasir A, Norton JD, Baou M, Zekavati A, Bijlmakers MJ et al. 2012. ZFP36L1 negatively regulates plasmacytoid differentiation of BCL1 cells by targeting BLIMP1 mRNA. PLOS ONE 7:e52187
    [Google Scholar]
  121. 121. 
    Newman R, Ahlfors H, Saveliev A, Galloway A, Hodson DJ et al. 2017. Maintenance of the marginal-zone B cell compartment specifically requires the RNA-binding protein ZFP36L1. Nat. Immunol. 18:683–93
    [Google Scholar]
  122. 122. 
    Salerno F, Engels S, van den Biggelaar M, van Alphen FPJ, Guislain A et al. 2018. Translational repression of pre-formed cytokine-encoding mRNA prevents chronic activation of memory T cells. Nat. Immunol. 19:828–37
    [Google Scholar]
  123. 123. 
    Sadri N, Lu JY, Badura ML, Schneider RJ. 2010. AUF1 is involved in splenic follicular B cell maintenance. BMC Immunol 11:1
    [Google Scholar]
  124. 124. 
    Sadri N, Schneider RJ. 2009. Auf1/Hnrnpd-deficient mice develop pruritic inflammatory skin disease. J. Investig. Dermatol. 129:657–70
    [Google Scholar]
  125. 125. 
    Kafer R, Schrick K, Schmidtke L, Montermann E, Hobernik D et al. 2017. Inactivation of the KSRP gene modifies collagen antibody induced arthritis. Mol. Immunol. 87:207–16
    [Google Scholar]
  126. 126. 
    Kafer R, Schmidtke L, Schrick K, Montermann E, Bros M et al. 2019. The RNA-binding protein KSRP modulates cytokine expression of CD4+ T cells. J. Immunol. Res. 2019:4726532
    [Google Scholar]
  127. 127. 
    Yu D, Tan AH, Hu X, Athanasopoulos V, Simpson N et al. 2007. Roquin represses autoimmunity by limiting inducible T-cell co-stimulator messenger RNA. Nature 450:299–303
    [Google Scholar]
  128. 128. 
    Lee SK, Silva DG, Martin JL, Pratama A, Hu X et al. 2012. Interferon-γ excess leads to pathogenic accumulation of follicular helper T cells and germinal centers. Immunity 37:880–92
    [Google Scholar]
  129. 129. 
    Stone EL, Pepper M, Katayama CD, Kerdiles YM, Lai CY et al. 2015. ICOS coreceptor signaling inactivates the transcription factor FOXO1 to promote Tfh cell differentiation. Immunity 42:239–51
    [Google Scholar]
  130. 130. 
    Essig K, Hu D, Guimaraes JC, Alterauge D, Edelmann S et al. 2017. Roquin suppresses the PI3K-mTOR signaling pathway to inhibit T helper cell differentiation and conversion of Treg to Tfr cells. Immunity 47:1067–82.e12
    [Google Scholar]
  131. 131. 
    Pratama A, Ramiscal RR, Silva DG, Das SK, Athanasopoulos V et al. 2013. Roquin-2 shares functions with its paralog Roquin-1 in the repression of mRNAs controlling T follicular helper cells and systemic inflammation. Immunity 38:669–80
    [Google Scholar]
  132. 132. 
    Vogel KU, Edelmann SL, Jeltsch KM, Bertossi A, Heger K et al. 2013. Roquin paralogs 1 and 2 redundantly repress the Icos and Ox40 costimulator mRNAs and control follicular helper T cell differentiation. Immunity 38:655–68
    [Google Scholar]
  133. 133. 
    Drees C, Vahl JC, Bortoluzzi S, Heger KD, Fischer JC et al. 2017. Roquin paralogs differentially regulate functional NKT cell subsets. J. Immunol. 198:2747–59
    [Google Scholar]
  134. 134. 
    Uehata T, Iwasaki H, Vandenbon A, Matsushita K, Hernandez-Cuellar E et al. 2013. Malt1-induced cleavage of Regnase-1 in CD4+ helper T cells regulates immune activation. Cell 153:1036–49
    [Google Scholar]
  135. 135. 
    Jeltsch KM, Hu D, Brenner S, Zoller J, Heinz GA et al. 2014. Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their cooperatively repressed targets to promote TH17 differentiation. Nat. Immunol. 15:1079–89
    [Google Scholar]
  136. 136. 
    Cui X, Mino T, Yoshinaga M, Nakatsuka Y, Hia F et al. 2017. Regnase-1 and Roquin nonredundantly regulate Th1 differentiation causing cardiac inflammation and fibrosis. J. Immunol. 199:4066–77
    [Google Scholar]
  137. 137. 
    Garg AV, Amatya N, Chen K, Cruz JA, Grover P et al. 2015. MCPIP1 endoribonuclease activity negatively regulates interleukin-17-mediated signaling and inflammation. Immunity 43:475–87
    [Google Scholar]
  138. 138. 
    Monin L, Gudjonsson JE, Childs EE, Amatya N, Xing X et al. 2017. MCPIP1/regnase-1 restricts IL-17A- and IL-17C-dependent skin inflammation. J. Immunol. 198:767–75
    [Google Scholar]
  139. 139. 
    Takaishi M, Satoh T, Akira S, Sano S. 2018. Regnase-1, an immunomodulator, limits the IL-36/IL-36R autostimulatory loop in keratinocytes to suppress skin inflammation. J. Investig. Dermatol. 138:1439–42
    [Google Scholar]
  140. 140. 
    Peng H, Ning H, Wang Q, Lu W, Chang Y et al. 2018. Monocyte chemotactic protein–induced protein 1 controls allergic airway inflammation by suppressing IL-5–producing TH2 cells through the Notch/Gata3 pathway. J. Allergy Clin. Immunol. 142:582–94.e10
    [Google Scholar]
  141. 141. 
    Matsushita K, Tanaka H, Yasuda K, Adachi T, Fukuoka A et al. 2020. Regnase-1 degradation is crucial for IL-33- and IL-25-mediated ILC2 activation. JCI Insight 5:4e131480
    [Google Scholar]
  142. 142. 
    Wei J, Long L, Zheng W, Dhungana Y, Lim SA et al. 2019. Targeting REGNASE-1 programs long-lived effector T cells for cancer therapy. Nature 576:471–76
    [Google Scholar]
  143. 143. 
    Tsoi LC, Spain SL, Knight J, Ellinghaus E, Stuart PE et al. 2012. Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nat. Genet. 44:1341–48
    [Google Scholar]
  144. 144. 
    von Gamm M, Schaub A, Jones AN, Wolf C, Behrens G et al. 2019. Immune homeostasis and regulation of the interferon pathway require myeloid-derived Regnase-3. J. Exp. Med. 216:1700–23
    [Google Scholar]
  145. 145. 
    Minagawa K, Wakahashi K, Kawano H, Nishikawa S, Fukui C et al. 2014. Posttranscriptional modulation of cytokine production in T cells for the regulation of excessive inflammation by TFL. J. Immunol. 192:1512–24
    [Google Scholar]
  146. 146. 
    Emming S, Bianchi N, Polletti S, Balestrieri C, Leoni C et al. 2020. A molecular network regulating the proinflammatory phenotype of human memory T lymphocytes. Nat. Immunol. 21:388–99
    [Google Scholar]
  147. 147. 
    Papadaki O, Milatos S, Grammenoudi S, Mukherjee N, Keene JD, Kontoyiannis DL. 2009. Control of thymic T cell maturation, deletion and egress by the RNA-binding protein HuR. J. Immunol. 182:6779–88
    [Google Scholar]
  148. 148. 
    Herjan T, Yao P, Qian W, Li X, Liu C et al. 2013. HuR is required for IL-17-induced Act1-mediated CXCL1 and CXCL5 mRNA stabilization. J. Immunol. 191:640–49
    [Google Scholar]
  149. 149. 
    Chen J, Martindale JL, Abdelmohsen K, Kumar G, Fortina PM et al. 2020. RNA-binding protein HuR promotes Th17 cell differentiation and can be targeted to reduce autoimmune neuroinflammation. J. Immunol. 204:2076–87
    [Google Scholar]
  150. 150. 
    Diaz-Munoz MD, Bell SE, Fairfax K, Monzon-Casanova E, Cunningham AF et al. 2015. The RNA-binding protein HuR is essential for the B cell antibody response. Nat. Immunol. 16:415–25
    [Google Scholar]
  151. 151. 
    Saito Y, Kagami S, Sanayama Y, Ikeda K, Suto A et al. 2014. AT-rich–interactive domain–containing protein 5A functions as a negative regulator of retinoic acid receptor–related orphan nuclear receptor γt–induced Th17 cell differentiation. Arthritis Rheumatol 66:1185–94
    [Google Scholar]
  152. 152. 
    Masuda K, Ripley B, Nyati KK, Dubey PK, Zaman MM et al. 2016. Arid5a regulates naive CD4+ T cell fate through selective stabilization of Stat3 mRNA. J. Exp. Med. 213:605–19
    [Google Scholar]
  153. 153. 
    Hanieh H, Masuda K, Metwally H, Chalise JP, Mohamed M et al. 2018. Arid5a stabilizes OX40 mRNA in murine CD4+ T cells by recognizing a stem-loop structure in its 3′UTR. Eur. J. Immunol. 48:593–604
    [Google Scholar]
  154. 154. 
    Amatya N, Childs EE, Cruz JA, Aggor FEY, Garg AV et al. 2018. IL-17 integrates multiple self-reinforcing, feed-forward mechanisms through the RNA binding protein Arid5a. Sci. Signal. 11:551eaat4617
    [Google Scholar]
  155. 155. 
    Moore MJ, Blachere NE, Fak JJ, Park CY, Sawicka K et al. 2018. ZFP36 RNA-binding proteins restrain T cell activation and anti-viral immunity. eLife 7:e33057
    [Google Scholar]
  156. 156. 
    Ebner F, Sedlyarov V, Tasciyan S, Ivin M, Kratochvill F et al. 2017. The RNA-binding protein tristetraprolin schedules apoptosis of pathogen-engaged neutrophils during bacterial infection. J. Clin. Investig. 127:2051–65
    [Google Scholar]
  157. 157. 
    Lin WJ, Zheng X, Lin CC, Tsao J, Zhu X et al. 2011. Posttranscriptional control of type I interferon genes by KSRP in the innate immune response against viral infection. Mol. Cell. Biol. 31:3196–207
    [Google Scholar]
  158. 158. 
    Paek KY, Kim CS, Park SM, Kim JH, Jang SK. 2008. RNA-binding protein hnRNP D modulates internal ribosome entry site-dependent translation of hepatitis C virus RNA. J. Virol. 82:12082–93
    [Google Scholar]
  159. 159. 
    Friedrich S, Schmidt T, Geissler R, Lilie H, Chabierski S et al. 2014. AUF1 p45 promotes West Nile virus replication by an RNA chaperone activity that supports cyclization of the viral genome. J. Virol. 88:11586–99
    [Google Scholar]
  160. 160. 
    Moore AE, Chenette DM, Larkin LC, Schneider RJ. 2014. Physiological networks and disease functions of RNA-binding protein AUF1. Wiley Interdiscip. Rev. RNA 5:549–64
    [Google Scholar]
  161. 161. 
    Lund N, Milev MP, Wong R, Sanmuganantham T, Woolaway K et al. 2012. Differential effects of hnRNP D/AUF1 isoforms on HIV-1 gene expression. Nucleic Acids Res 40:3663–75
    [Google Scholar]
  162. 162. 
    Lee N, Pimienta G, Steitz JA. 2012. AUF1/hnRNP D is a novel protein partner of the EBER1 noncoding RNA of Epstein-Barr virus. RNA 18:2073–82
    [Google Scholar]
  163. 163. 
    Albornoz A, Carletti T, Corazza G, Marcello A 2014. The stress granule component TIA-1 binds tick-borne encephalitis virus RNA and is recruited to perinuclear sites of viral replication to inhibit viral translation. J. Virol. 88:6611–22
    [Google Scholar]
  164. 164. 
    Song J, Lee S, Cho DY, Lee S, Kim H et al. 2019. Human cytomegalovirus induces and exploits Roquin to counteract the IRF1-mediated antiviral state. PNAS 116:18619–28
    [Google Scholar]
  165. 165. 
    Lin RJ, Chien HL, Lin SY, Chang BL, Yu HP et al. 2013. MCPIP1 ribonuclease exhibits broad-spectrum antiviral effects through viral RNA binding and degradation. Nucleic Acids Res 41:3314–26
    [Google Scholar]
  166. 166. 
    Happel C, Ramalingam D, Ziegelbauer JM. 2016. Virus-mediated alterations in miRNA factors and degradation of viral miRNAs by MCPIP1. PLOS Biol 14:e2000998
    [Google Scholar]
  167. 167. 
    Qian L, Zuo Y, Deng W, Miao Y, Liu J et al. 2018. MCPIP1 is a positive regulator of type I interferons antiviral activity. Biochem. Biophys. Res. Commun. 498:891–97
    [Google Scholar]
  168. 168. 
    Sun X, Feng W, Guo Y, Wang Q, Dong C et al. 2018. MCPIP1 attenuates the innate immune response to influenza A virus by suppressing RIG-I expression in lung epithelial cells. J. Med. Virol. 90:204–11
    [Google Scholar]
  169. 169. 
    Nakatsuka Y, Vandenbon A, Mino T, Yoshinaga M, Uehata T et al. 2018. Pulmonary Regnase-1 orchestrates the interplay of epithelium and adaptive immune systems to protect against pneumonia. Mucosal Immunol 11:1203–18
    [Google Scholar]
  170. 170. 
    Sueyoshi T, Kawasaki T, Kitai Y, Ori D, Akira S, Kawai T. 2018. Hu antigen R regulates antiviral innate immune responses through the stabilization of mRNA for Polo-like kinase 2. J. Immunol. 200:3814–24
    [Google Scholar]
  171. 171. 
    Zainol MIB, Kawasaki T, Monwan W, Murase M, Sueyoshi T, Kawai T. 2019. Innate immune responses through Toll-like receptor 3 require human-antigen-R-mediated Atp6v0d2 mRNA stabilization. Sci. Rep. 9:20406
    [Google Scholar]
  172. 172. 
    Park JM, Lee TH, Kang TH. 2018. Roles of tristetraprolin in tumorigenesis. Int. J. Mol. Sci. 19:113384
    [Google Scholar]
  173. 173. 
    Rounbehler RJ, Fallahi M, Yang C, Steeves MA, Li W et al. 2012. Tristetraprolin impairs myc-induced lymphoma and abolishes the malignant state. Cell 150:563–74
    [Google Scholar]
  174. 174. 
    Hodson DJ, Janas ML, Galloway A, Bell SE, Andrews S et al. 2010. Deletion of the RNA-binding proteins ZFP36L1 and ZFP36L2 leads to perturbed thymic development and T lymphoblastic leukemia. Nat. Immunol. 11:717–24
    [Google Scholar]
  175. 175. 
    Abba MC, Sun H, Hawkins KA, Drake JA, Hu Y et al. 2007. Breast cancer molecular signatures as determined by SAGE: correlation with lymph node status. Mol. Cancer Res. 5:881–90
    [Google Scholar]
  176. 176. 
    Montero J, Gstalder C, Kim DJ, Sadowicz D, Miles W et al. 2019. Destabilization of NOXA mRNA as a common resistance mechanism to targeted therapies. Nat. Commun. 10:5157
    [Google Scholar]
  177. 177. 
    Krohler T, Kessler SM, Hosseini K, List M, Barghash A et al. 2019. The mRNA-binding protein TTP/ZFP36 in hepatocarcinogenesis and hepatocellular carcinoma. Cancers 11:111754
    [Google Scholar]
  178. 178. 
    Lopez de Silanes I, Quesada MP, Esteller M. 2007. Aberrant regulation of messenger RNA 3′-untranslated region in human cancer. Cell Oncol 29:1–17
    [Google Scholar]
  179. 179. 
    Zhang X, Wan G, Berger FG, He X, Lu X. 2011. The ATM kinase induces microRNA biogenesis in the DNA damage response. Mol. Cell 41:371–83
    [Google Scholar]
  180. 180. 
    Ellyard JI, Chia T, Rodriguez-Pinilla SM, Martin JL, Hu X et al. 2012. Heterozygosity for Roquinsan leads to angioimmunoblastic T-cell lymphoma-like tumors in mice. Blood 120:812–21
    [Google Scholar]
  181. 181. 
    Choi J, Zhou N, Busino L. 2019. KLHL6 is a tumor suppressor gene in diffuse large B-cell lymphoma. Cell Cycle 18:249–56
    [Google Scholar]
  182. 182. 
    Zhou L, Azfer A, Niu J, Graham S, Choudhury M et al. 2006. Monocyte chemoattractant protein-1 induces a novel transcription factor that causes cardiac myocyte apoptosis and ventricular dysfunction. Circ. Res. 98:1177–85
    [Google Scholar]
  183. 183. 
    Kidoya H, Muramatsu F, Shimamura T, Jia W, Satoh T et al. 2019. Regnase-1-mediated post-transcriptional regulation is essential for hematopoietic stem and progenitor cell homeostasis. Nat. Commun. 10:1072
    [Google Scholar]
  184. 184. 
    Minagawa K, Yamamoto K, Nishikawa S, Ito M, Sada A et al. 2007. Deregulation of a possible tumour suppressor gene, ZC3H12D, by translocation of IGK@ in transformed follicular lymphoma with t(2;6)(p12;q25). Br. J. Haematol. 139:161–63
    [Google Scholar]
  185. 185. 
    Mazan-Mamczarz K, Hagner PR, Corl S, Srikantan S, Wood WH et al. 2008. Post-transcriptional gene regulation by HuR promotes a more tumorigenic phenotype. Oncogene 27:6151–63
    [Google Scholar]
  186. 186. 
    Abdelmohsen K, Gorospe M. 2010. Posttranscriptional regulation of cancer traits by HuR. Wiley Interdiscip. Rev. RNA 1:214–29
    [Google Scholar]
  187. 187. 
    Calaluce R, Gubin MM, Davis JW, Magee JD, Chen J et al. 2010. The RNA binding protein HuR differentially regulates unique subsets of mRNAs in estrogen receptor negative and estrogen receptor positive breast cancer. BMC Cancer 10:126
    [Google Scholar]
  188. 188. 
    Gubin MM, Calaluce R, Davis JW, Magee JD, Strouse CS et al. 2010. Overexpression of the RNA binding protein HuR impairs tumor growth in triple negative breast cancer associated with deficient angiogenesis. Cell Cycle 9:3337–46
    [Google Scholar]
  189. 189. 
    Ortega AD, Sala S, Espinosa E, Gonzalez-Baron M, Cuezva JM. 2008. HuR and the bioenergetic signature of breast cancer: a low tumor expression of the RNA-binding protein predicts a higher risk of disease recurrence. Carcinogenesis 29:2053–61
    [Google Scholar]
  190. 190. 
    Richards NG, Rittenhouse DW, Freydin B, Cozzitorto JA, Grenda D et al. 2010. HuR status is a powerful marker for prognosis and response to gemcitabine-based chemotherapy for resected pancreatic ductal adenocarcinoma patients. Ann. Surg. 252:499–505
    [Google Scholar]
  191. 191. 
    Costantino CL, Witkiewicz AK, Kuwano Y, Cozzitorto JA, Kennedy EP et al. 2009. The role of HuR in gemcitabine efficacy in pancreatic cancer: HuR up-regulates the expression of the gemcitabine metabolizing enzyme deoxycytidine kinase. Cancer Res 69:4567–72
    [Google Scholar]
  192. 192. 
    Eshelman MA, Matthews SM, Schleicher EM, Fleeman RM, Kawasawa YI et al. 2019. Tristetraprolin targets Nos2 expression in the colonic epithelium. Sci. Rep. 9:14413
    [Google Scholar]
  193. 193. 
    Nagahama Y, Shimoda M, Mao G, Singh SK, Kozakai Y et al. 2018. Regnase-1 controls colon epithelial regeneration via regulation of mTOR and purine metabolism. PNAS 115:11036–41
    [Google Scholar]
  194. 194. 
    Kakiuchi N, Yoshida K, Uchino M, Kihara T, Akaki K et al. 2020. Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis. Nature 577:260–65
    [Google Scholar]
  195. 195. 
    Nanki K, Fujii M, Shimokawa M, Matano M, Nishikori S et al. 2020. Somatic inflammatory gene mutations in human ulcerative colitis epithelium. Nature 577:254–59
    [Google Scholar]
  196. 196. 
    Olafsson S, McIntyre RE, Coorens T, Butler T, Jung H et al. 2020. Somatic evolution in non-neoplastic IBD-affected colon. Cell 182:672–84.e11
    [Google Scholar]
  197. 197. 
    Liu L, Christodoulou-Vafeiadou E, Rao JN, Zou T, Xiao L et al. 2014. RNA-binding protein HuR promotes growth of small intestinal mucosa by activating the Wnt signaling pathway. Mol. Biol. Cell 25:3308–18
    [Google Scholar]
  198. 198. 
    Yu TX, Gu BL, Yan JK, Zhu J, Yan WH et al. 2016. CUGBP1 and HuR regulate E-cadherin translation by altering recruitment of E-cadherin mRNA to processing bodies and modulate epithelial barrier function. Am. J. Physiol. Cell Physiol. 310:C54–65
    [Google Scholar]
  199. 199. 
    Zhuang R, Rao JN, Zou T, Liu L, Xiao L et al. 2013. miR-195 competes with HuR to modulate stim1 mRNA stability and regulate cell migration. Nucleic Acids Res 41:7905–19
    [Google Scholar]
  200. 200. 
    Giammanco A, Blanc V, Montenegro G, Klos C, Xie Y et al. 2014. Intestinal epithelial HuR modulates distinct pathways of proliferation and apoptosis and attenuates small intestinal and colonic tumor development. Cancer Res 74:5322–35
    [Google Scholar]
  201. 201. 
    Yiakouvaki A, Dimitriou M, Karakasiliotis I, Eftychi C, Theocharis S, Kontoyiannis DL. 2012. Myeloid cell expression of the RNA-binding protein HuR protects mice from pathologic inflammation and colorectal carcinogenesis. J. Clin. Investig. 122:48–61
    [Google Scholar]
  202. 202. 
    Sawicki KT, Chang HC, Shapiro JS, Bayeva M, De Jesus A et al. 2018. Hepatic tristetraprolin promotes insulin resistance through RNA destabilization of FGF21. JCI Insight 3:13e95948
    [Google Scholar]
  203. 203. 
    Tarling EJ, Clifford BL, Cheng J, Morand P, Cheng A et al. 2017. RNA-binding protein ZFP36L1 maintains posttranscriptional regulation of bile acid metabolism. J. Clin. Investig. 127:3741–54
    [Google Scholar]
  204. 204. 
    Bayeva M, Khechaduri A, Puig S, Chang HC, Patial S et al. 2012. mTOR regulates cellular iron homeostasis through tristetraprolin. Cell Metab 16:645–57
    [Google Scholar]
  205. 205. 
    Sato T, Chang HC, Bayeva M, Shapiro JS, Ramos-Alonso L et al. 2018. mRNA-binding protein tristetraprolin is essential for cardiac response to iron deficiency by regulating mitochondrial function. PNAS 115:E6291–300
    [Google Scholar]
  206. 206. 
    Chou CF, Lin YY, Wang HK, Zhu X, Giovarelli M et al. 2014. KSRP ablation enhances brown fat gene program in white adipose tissue through reduced miR-150 expression. Diabetes 63:2949–61
    [Google Scholar]
  207. 207. 
    Lin YY, Chou CF, Giovarelli M, Briata P, Gherzi R, Chen CY. 2014. KSRP and microRNA 145 are negative regulators of lipolysis in white adipose tissue. Mol. Cell. Biol. 34:2339–49
    [Google Scholar]
  208. 208. 
    Chou CF, Zhu X, Lin YY, Gamble KL, Garvey WT, Chen CY. 2015. KSRP is critical in governing hepatic lipid metabolism through controlling Per2 expression. J. Lipid Res. 56:227–40
    [Google Scholar]
  209. 209. 
    Yoshinaga M, Nakatsuka Y, Vandenbon A, Ori D, Uehata T et al. 2017. Regnase-1 maintains iron homeostasis via the degradation of transferrin receptor 1 and prolyl-hydroxylase-domain-containing protein 3 mRNAs. Cell Rep 19:1614–30
    [Google Scholar]
  210. 210. 
    Younce CW, Azfer A, Kolattukudy PE. 2009. MCP-1 (monocyte chemotactic protein-1)-induced protein, a recently identified zinc finger protein, induces adipogenesis in 3T3-L1 pre-adipocytes without peroxisome proliferator-activated receptor γ. J. Biol. Chem. 284:27620–28
    [Google Scholar]
  211. 211. 
    Lipert B, Wegrzyn P, Sell H, Eckel J, Winiarski M et al. 2014. Monocyte chemoattractant protein-induced protein 1 impairs adipogenesis in 3T3-L1 cells. Biochim. Biophys. Acta Mol. Cell Res. 1843:780–88
    [Google Scholar]
  212. 212. 
    Losko M, Dolicka D, Pydyn N, Jankowska U, Kedracka-Krok S et al. 2020. Integrative genomics reveal a role for MCPIP1 in adipogenesis and adipocyte metabolism. Cell Mol. Life Sci. 77:234899–919 https://doi.org/10.1007/s00018-019-03434-5
    [Crossref] [Google Scholar]
  213. 213. 
    Habacher C, Guo Y, Venz R, Kumari P, Neagu A et al. 2016. Ribonuclease-mediated control of body fat. Dev. Cell 39:359–69
    [Google Scholar]
  214. 214. 
    Ramirez CM, Lin CS, Abdelmohsen K, Goedeke L, Yoon JH et al. 2014. RNA binding protein HuR regulates the expression of ABCA1. J. Lipid Res. 55:1066–76
    [Google Scholar]
  215. 215. 
    Chalise JP, Hashimoto S, Parajuli G, Kang S, Singh SK et al. 2019. Feedback regulation of Arid5a and Ppar-γ2 maintains adipose tissue homeostasis. PNAS 116:15128–33
    [Google Scholar]
  216. 216. 
    Meisner NC, Hintersteiner M, Mueller K, Bauer R, Seifert JM et al. 2007. Identification and mechanistic characterization of low-molecular-weight inhibitors for HuR. Nat. Chem. Biol. 3:508–15
    [Google Scholar]
  217. 217. 
    Bollmann F, Art J, Henke J, Schrick K, Besche V et al. 2014. Resveratrol post-transcriptionally regulates pro-inflammatory gene expression via regulation of KSRP RNA binding activity. Nucleic Acids Res 42:12555–69
    [Google Scholar]
  218. 218. 
    Lang M, Berry D, Passecker K, Mesteri I, Bhuju S et al. 2017. HuR small-molecule inhibitor elicits differential effects in adenomatosis polyposis and colorectal carcinogenesis. Cancer Res 77:2424–38
    [Google Scholar]
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