Post-transcriptional regulatory networks in immunity

Immunological Reviews

Volumn 253, Issue 1, 2013, Pages 253-272

  Ivanov, Pavel ^a,b   Anderson, Paul ^a,b  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Inflammation; MicroRNAs; MRNA decay; Post transcriptional regulation; RNA binding proteins; Translational control

Indexed keywords

BETA INTERFERON; CD40 LIGAND; CD9 ANTIGEN; CERULOPLASMIN; CXCL1 CHEMOKINE; CXCL2 CHEMOKINE; CXCL3 CHEMOKINE; CYCLOOXYGENASE 2; GAMMA INTERFERON; GAMMA INTERFERON INDUCIBLE PROTEIN 10; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; I KAPPA B ALPHA; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERFERON REGULATORY FACTOR 1; INTERLEUKIN 10; INTERLEUKIN 11; INTERLEUKIN 12P40; INTERLEUKIN 13; INTERLEUKIN 17; INTERLEUKIN 18; INTERLEUKIN 1BETA; INTERLEUKIN 2; INTERLEUKIN 3; INTERLEUKIN 4; INTERLEUKIN 6; INTERLEUKIN 8; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; MESSENGER RNA; MONOCYTE CHEMOTACTIC PROTEIN 1 INHIBITOR; UNINDEXED DRUG;

AUTOIMMUNE DISEASE; CELLULAR DISTRIBUTION; HUMAN; IMMUNE RESPONSE; IMMUNITY; IMMUNOMODULATION; MOLECULAR INTERACTION; MOLECULAR MECHANICS; NONSENSE MEDIATED MRNA DECAY; PRIORITY JOURNAL; REVIEW; RNA DEGRADATION; RNA METABOLISM; RNA STABILITY; RNA TRANSLATION; TRANSCRIPTION REGULATION; TRANSLATION REGULATION;

3' UNTRANSLATED REGIONS; ANIMALS; AUTOIMMUNE DISEASES; GENE EXPRESSION REGULATION; HUMANS; LYMPHOCYTES; RNA INTERFERENCE; RNA-BINDING PROTEINS;

EID: 84875781795     PISSN: 01052896     EISSN: 1600065X     Source Type: Journal    
DOI: 10.1111/imr.12051     Document Type: Review

References (244)

1. Schmid M, Jensen TH. Nuclear quality control of RNA polymerase II transcripts. Wiley Interdiscip Rev RNA 2010;1:474-485.
2. Goldstrohm AC, Wickens M. Multifunctional deadenylase complexes diversify mRNA control. Nat Rev Mol Cell Biol 2008;9:337-344.
3. Chen CY, Shyu AB. Mechanisms of deadenylation-dependent decay. Wiley Interdiscip Rev RNA 2011;2:167-183.
4. Yamashita A, et al. Concerted action of poly(A) nucleases and decapping enzyme in mammalian mRNA turnover. Nat Struct Mol Biol 2005;12:1054-1063.
5. Ling SH, Qamra R, Song H. Structural and functional insights into eukaryotic mRNA decapping. Wiley Interdiscip Rev RNA 2011;2:193-208.
6. Caput D, Beutler B, Hartog K, Thayer R, Brown-Shimer S, Cerami A. Identification of a common nucleotide sequence in the 3′-untranslated region of mRNA molecules specifying inflammatory mediators. Proc Natl Acad Sci USA 1986;83:1670-1674.
7. Shaw G, Kamen R. A conserved AU sequence from the 3′ untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell 1986;46:659-667.
8. Kontoyiannis D, Pasparakis M, Pizarro TT, Cominelli F, Kollias G. Impaired on/off regulation of TNF biosynthesis in mice lacking TNF AU-rich elements: implications for joint and gut-associated immunopathologies. Immunity 1999;10:387-398.
9. Stoecklin G, Hahn S, Moroni C. Functional hierarchy of AUUUA motifs in mediating rapid interleukin-3 mRNA decay. J Biol Chem 1994;269:28591-28597.
10. Chen CY, Shyu AB. AU-rich elements: characterization and importance in mRNA degradation. Trends Biochem Sci 1995;20:465-470.
11. Chen CY, Xu N, Shyu AB. mRNA decay mediated by two distinct AU-rich elements from c-fos and granulocyte-macrophage colony-stimulating factor transcripts: different deadenylation kinetics and uncoupling from translation. Mol Cell Biol 1995;15:5777-5788.
12. Lagnado CA, Brown CY, Goodall GJ. AUUUA is not sufficient to promote poly(A) shortening and degradation of an mRNA: the functional sequence within AU-rich elements may be UUAUUUA(U/A)(U/A). Mol Cell Biol 1994;14:7984-7995.
13. Zubiaga AM, Belasco JG, Greenberg ME. The nonamer UUAUUUAUU is the key AU-rich sequence motif that mediates mRNA degradation. Mol Cell Biol 1995;15:2219-2230.
14. Bakheet T, Williams BR, Khabar KS. ARED 3.0: the large and diverse AU-rich transcriptome. Nucleic Acids Res 2006;34:D111-D114.
15. Carballo E, Lai WS, Blackshear PJ. Feedback inhibition of macrophage tumor necrosis factor-alpha production by tristetraprolin. Science 1998;281:1001-1005.
16. Stoecklin G, et al. Functional cloning of BRF1, a regulator of ARE-dependent mRNA turnover. EMBO J 2002;21:4709-4718.
17. Hinman MN, Lou H. Diverse molecular functions of Hu proteins. Cell Mol Life Sci 2008;65:3168-3181.
18. Gratacos FM, Brewer G. The role of AUF1 in regulated mRNA decay. Wiley Interdiscip Rev RNA 2010;1:457-473.
19. Piecyk M, et al. TIA-1 is a translational silencer that selectively regulates the expression of TNF-alpha. EMBO J 2000;19:4154-4163.
20. Briata P, et al. KSRP, many functions for a single protein. Front Biosci 2011;16:1787-1796.
21. Garnon J, et al. Fragile X-related protein FXR1P regulates proinflammatory cytokine tumor necrosis factor expression at the post-transcriptional level. J Biol Chem 2005;280:5750-5763.
22. Chen CY, et al. Nucleolin and YB-1 are required for JNK-mediated interleukin-2 mRNA stabilization during T-cell activation. Genes Dev 2000;14:1236-1248.
23. Mukhopadhyay D, Houchen CW, Kennedy S, Dieckgraefe BK, Anant S. Coupled mRNA stabilization and translational silencing of cyclooxygenase-2 by a novel RNA binding protein, CUGBP2. Mol Cell 2003;11:113-126.
24. Mukhopadhyay D, Jung J, Murmu N, Houchen CW, Dieckgraefe BK, Anant S. CUGBP2 plays a critical role in apoptosis of breast cancer cells in response to genotoxic injury. Ann NY Acad Sci USA 2003;1010:504-509.
25. Gherzi R, et al. A KH domain RNA binding protein, KSRP, promotes ARE-directed mRNA turnover by recruiting the degradation machinery. Mol Cell 2004;14:571-583.
26. Laroia G, Cuesta R, Brewer G, Schneider RJ. Control of mRNA decay by heat shock-ubiquitin-proteasome pathway. Science 1999;284:499-502.
27. Lu JY, Sadri N, Schneider RJ. Endotoxic shock in AUF1 knockout mice mediated by failure to degrade proinflammatory cytokine mRNAs. Genes Dev 2006;20:3174-3184.
28. Sarkar B, Xi Q, He C, Schneider RJ. Selective degradation of AU-rich mRNAs promoted by the p37 AUF1 protein isoform. Mol Cell Biol 2003;23:6685-6693.
29. Fan XC, Steitz JA. Overexpression of HuR, a nuclear-cytoplasmic shuttling protein, increases the in vivo stability of ARE-containing mRNAs. EMBO J 1998;17:3448-3460.
30. Peng SS, Chen CY, Xu N, Shyu AB. RNA stabilization by the AU-rich element binding protein, HuR, an ELAV protein. EMBO J 1998;17:3461-3470.
31. Galban S, et al. RNA-binding proteins HuR and PTB promote the translation of hypoxia-inducible factor 1alpha. Mol Cell Biol 2008;28:93-107.
32. Katsanou V, et al. HuR as a negative posttranscriptional modulator in inflammation. Mol Cell 2005;19:777-789.
33. David PS, Tanveer R, Port JD. FRET-detectable interactions between the ARE binding proteins, HuR and p37AUF1. RNA 2007;13:1453-1468.
34. Kawai T, Lal A, Yang X, Galban S, Mazan-Mamczarz K, Gorospe M. Translational control of cytochrome c by RNA-binding proteins TIA-1 and HuR. Mol Cell Biol 2006;26:3295-3307.
35. Linker K, Pautz A, Fechir M, Hubrich T, Greeve J, Kleinert H. Involvement of KSRP in the post-transcriptional regulation of human iNOS expression-complex interplay of KSRP with TTP and HuR. Nucleic Acids Res 2005;33:4813-4827.
36. Pan YX, Chen H, Kilberg MS. Interaction of RNA-binding proteins HuR and AUF1 with the human ATF3 mRNA 3′-untranslated region regulates its amino acid limitation-induced stabilization. J Biol Chem 2005;280:34609-34616.
37. Sureban SM, et al. Functional antagonism between RNA binding proteins HuR and CUGBP2 determines the fate of COX-2 mRNA translation. Gastroenterology 2007;132:1055-1065.
38. Pastore S, Mascia F, Mariotti F, Dattilo C, Mariani V, Girolomoni G. ERK1/2 regulates epidermal chemokine expression and skin inflammation. J Immunol 2005;174:5047-5056.
39. Sauer I, et al. Interferons limit inflammatory responses by induction of tristetraprolin. Blood 2006;107:4790-4797.
40. Marcais A, Tomkowiak M, Walzer T, Coupet CA, Ravel-Chapuis A, Marvel J. Maintenance of CCL5 mRNA stores by post-effector and memory CD8 T cells is dependent on transcription and is coupled to increased mRNA stability. Eur J Immunol 2006;36:2745-2754.
41. Atasoy U, et al. Regulation of eotaxin gene expression by TNF-alpha and IL-4 through mRNA stabilization: involvement of the RNA-binding protein HuR. J Immunol 2003;171:4369-4378.
42. Arif A, Jia J, Mukhopadhyay R, Willard B, Kinter M, Fox PL. Two-site phosphorylation of EPRS coordinates multimodal regulation of noncanonical translational control activity. Mol Cell 2009;35:164-180.
43. Vlasova IA, et al. Conserved GU-rich elements mediate mRNA decay by binding to CUG-binding protein 1. Mol Cell 2008;29:263-270.
44. Barnhart B, Kosinski PA, Wang Z, Ford GS, Kiledjian M, Covey LR. Identification of a complex that binds to the CD154 3′ untranslated region: implications for a role in message stability during T cell activation. J Immunol 2000;165:4478-4486.
45. Ford GS, Barnhart B, Shone S, Covey LR. Regulation of CD154 (CD40 ligand) mRNA stability during T cell activation. J Immunol 1999;162:4037-4044.
46. Hamilton BJ, Genin A, Cron RQ, Rigby WF. Delineation of a novel pathway that regulates CD154 (CD40 ligand) expression. Mol Cell Biol 2003;23:510-525.
47. Hamilton BJ, et al. Separate cis-trans pathways post-transcriptionally regulate murine CD154 (CD40 ligand) expression: a novel function for CA repeats in the 3′-untranslated region. J Biol Chem 2008;283:25606-25616.
48. Kosinski PA, Laughlin J, Singh K, Covey LR. A complex containing polypyrimidine tract-binding protein is involved in regulating the stability of CD40 ligand (CD154) mRNA. J Immunol 2003;170:979-988.
49. Rigby WF, Waugh MG, Hamilton BJ. Characterization of RNA binding proteins associated with CD40 ligand (CD154) mRNA turnover in human T lymphocytes. J Immunol 1999;163:4199-4206.
50. Singh K, Laughlin J, Kosinski PA, Covey LR. Nucleolin is a second component of the CD154 mRNA stability complex that regulates mRNA turnover in activated T cells. J Immunol 2004;173:976-985.
51. Vavassori S, Shi Y, Chen CC, Ron Y, Covey LR. In vivo post-transcriptional regulation of CD154 in mouse CD4 + T cells. Eur J Immunol 2009;39:2224-2232.
52. Mazumder B, Fox PL. Delayed translational silencing of ceruloplasmin transcript in gamma interferon-activated U937 monocytic cells: role of the 3′ untranslated region. Mol Cell Biol 1999;19:6898-6905.
53. Cok SJ, Acton SJ, Morrison AR. The proximal region of the 3′-untranslated region of cyclooxygenase-2 is recognized by a multimeric protein complex containing HuR, TIA-1, TIAR, and the heterogeneous nuclear ribonucleoprotein U. J Biol Chem 2003;278:36157-36162.
54. Dixon DA, et al. Regulation of cyclooxygenase-2 expression by the translational silencer TIA-1. J Exp Med 2003;198:475-481.
55. Datta S, et al. Tristetraprolin regulates CXCL1 (KC) mRNA stability. J Immunol 2008;180:2545-2552.
56. Rousseau S, Morrice N, Peggie M, Campbell DG, Gaestel M, Cohen P. Inhibition of SAPK2a/p38 prevents hnRNP A0 phosphorylation by MAPKAP-K2 and its interaction with cytokine mRNAs. EMBO J 2002;21:6505-6514.
57. Stoeckle MY. Post-transcriptional regulation of gro alpha, beta, gamma, and IL-8 mRNAs by IL-1 beta. Nucleic Acids Res 1991;19:917-920.
58. Vockerodt M, et al. The Epstein-Barr virus oncoprotein latent membrane protein 1 induces expression of the chemokine IP-10: importance of mRNA half-life regulation. Int J Cancer 2005;114:598-605.
59. Frasca D, Landin AM, Alvarez JP, Blackshear PJ, Riley RL, Blomberg BB. Tristetraprolin, a negative regulator of mRNA stability, is increased in old B cells and is involved in the degradation of E47 mRNA. J Immunol 2007;179:918-927.
60. Brown CY, Lagnado CA, Goodall GJ. A cytokine mRNA-destabilizing element that is structurally and functionally distinct from A+U-rich elements. Proc Natl Acad Sci USA 1996;93:13721-13725.
61. Koeffler HP, Gasson J, Tobler A. Transcriptional and posttranscriptional modulation of myeloid colony-stimulating factor expression by tumor necrosis factor and other agents. Mol Cell Biol 1988;8:3432-3438.
62. Putland RA, et al. RNA destabilization by the granulocyte colony-stimulating factor stem-loop destabilizing element involves a single stem-loop that promotes deadenylation. Mol Cell Biol 2002;22:1664-1673.
63. Bickel M, Cohen RB, Pluznik DH. Post-transcriptional regulation of granulocyte-macrophage colony-stimulating factor synthesis in murine T cells. J Immunol 1990;145:840-845.
64. Carballo E, Lai WS, Blackshear PJ. Evidence that tristetraprolin is a physiological regulator of granulocyte-macrophage colony-stimulating factor messenger RNA deadenylation and stability. Blood 2000;95:1891-1899.
65. Esnault S, Shen ZJ, Whitesel E, Malter JS. The peptidyl-prolyl isomerase Pin1 regulates granulocyte-macrophage colony-stimulating factor mRNA stability in T lymphocytes. J Immunol 2006;177:6999-7006.
66. Grosset C, Boniface R, Duchez P, Solanilla A, Cosson B, Ripoche J. In vivo studies of translational repression mediated by the granulocyte-macrophage colony-stimulating factor AU-rich element. J Biol Chem 2004;279:13354-13362.
67. Yu D, et al. Roquin represses autoimmunity by limiting inducible T-cell co-stimulator messenger RNA. Nature 2007;450:299-303.
68. Lin WJ, et al. Posttranscriptional control of type I interferon genes by KSRP in the innate immune response against viral infection. Mol Cell Biol 2011;31:3196-3207.
69. Raj NB, Pitha PM. Two levels of regulation of beta-interferon gene expression in human cells. Proc Natl Acad Sci USA 1983;80:3923-3927.
70. Whittemore LA, Maniatis T. Postinduction repression of the beta-interferon gene is mediated through two positive regulatory domains. Proc Natl Acad Sci USA 1990;87:7799-7803.
71. Hodge DL, Martinez A, Julias JG, Taylor LS, Young HA. Regulation of nuclear gamma interferon gene expression by interleukin 12 (IL-12) and IL-2 represents a novel form of posttranscriptional control. Mol Cell Biol 2002;22:1742-1753.
72. Mavropoulos A, Sully G, Cope AP, Clark AR. Stabilization of IFN-gamma mRNA by MAPK p38 in IL-12- and IL-18-stimulated human NK cells. Blood 2005;105:282-288.
73. Wang JG, et al. LFA-1-dependent HuR nuclear export and cytokine mRNA stabilization in T cell activation. J Immunol 2006;176:2105-2113.
74. Hao S, Baltimore D. The stability of mRNA influences the temporal order of the induction of genes encoding inflammatory molecules. Nat Immunol 2009;10:281-288.
75. Chen YL, Huang YL, Lin NY, Chen HC, Chiu WC, Chang CJ. Differential regulation of ARE-mediated TNFalpha and IL-1beta mRNA stability by lipopolysaccharide in RAW264.7 cells. Biochem Biophys Res Commun 2006;346:160-168.
76. Fenton MJ, Vermeulen MW, Clark BD, Webb AC, Auron PE. Human pro-IL-1 beta gene expression in monocytic cells is regulated by two distinct pathways. J Immunol 1988;140:2267-2273.
77. Mizgalska D, et al. Interleukin-1-inducible MCPIP protein has structural and functional properties of RNase and participates in degradation of IL-1beta mRNA. FEBS J 2009;276:7386-7399.
78. Sirenko OI, Lofquist AK, DeMaria CT, Morris JS, Brewer G, Haskill JS. Adhesion-dependent regulation of an A+U-rich element-binding activity associated with AUF1. Mol Cell Biol 1997;17:3898-3906.
79. Bufler P, Gamboni-Robertson F, Azam T, Kim SH, Dinarello CA. Interleukin-1 homologues IL-1F7b and IL-18 contain functional mRNA instability elements within the coding region responsive to lipopolysaccharide. Biochem J 2004;381:503-510.
80. Ogilvie RL, Abelson M, Hau HH, Vlasova I, Blackshear PJ, Bohjanen PR. Tristetraprolin down-regulates IL-2 gene expression through AU-rich element-mediated mRNA decay. J Immunol 2005;174:953-961.
81. Shi L, Godfrey WR, Lin J, Zhao G, Kao PN. NF90 regulates inducible IL-2 gene expression in T cells. J Exp Med 2007;204:971-977.
82. Shim J, Lim H. J RY, Karin M. Nuclear export of NF90 is required for interleukin-2 mRNA stabilization. Mol Cell 2002;10:1331-1344.
83. Nair AP, Hahn S, Banholzer R, Hirsch HH, Moroni C. Cyclosporin A inhibits growth of autocrine tumour cell lines by destabilizing interleukin-3 mRNA. Nature 1994;369:239-242.
84. Stoecklin G, Ming XF, Looser R, Moroni C. Somatic mRNA turnover mutants implicate tristetraprolin in the interleukin-3 mRNA degradation pathway. Mol Cell Biol 2000;20:3753-3763.
85. Wodnar-Filipowicz A, Moroni C. Regulation of interleukin 3 mRNA expression in mast cells occurs at the posttranscriptional level and is mediated by calcium ions. Proc Natl Acad Sci USA 1990;87:777-781.
86. Yarovinsky TO, Butler NS, Monick MM, Hunninghake GW. Early exposure to IL-4 stabilizes IL-4 mRNA in CD4 + T cells via RNA-binding protein HuR. J Immunol 2006;177:4426-4435.
87. Akashi M, Loussararian AH, Adelman DC, Saito M, Koeffler HP. Role of lymphotoxin in expression of interleukin 6 in human fibroblasts. Stimulation and regulation. J Clin Invest 1990;85:121-129.
88. Jones MR, et al. Zcchc11-dependent uridylation of microRNA directs cytokine expression. Nat Cell Biol 2009;11:1157-1163.
89. Matsushita K, et al. Zc3h12a is an RNase essential for controlling immune responses by regulating mRNA decay. Nature 2009;458:1185-1190.
90. Neininger A, et al. MK2 targets AU-rich elements and regulates biosynthesis of tumor necrosis factor and interleukin-6 independently at different post-transcriptional levels. J Biol Chem 2002;277:3065-3068.
91. Paschoud S, Dogar AM, Kuntz C, Grisoni-Neupert B, Richman L, Kuhn LC. 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 2006;26:8228-8241.
92. Winzen R, et al. The p38 MAP kinase pathway signals for cytokine-induced mRNA stabilization via MAP kinase-activated protein kinase 2 and an AU-rich region-targeted mechanism. EMBO J 1999;18:4969-4980.
93. Winzen R, et al. Functional analysis of KSRP interaction with the AU-rich element of interleukin-8 and identification of inflammatory mRNA targets. Mol Cell Biol 2007;27:8388-8400.
94. Stoecklin G, et al. Genome-wide analysis identifies interleukin-10 mRNA as target of tristetraprolin. J Biol Chem 2008;283:11689-11699.
95. Bamba S, Andoh A, Yasui H, Makino J, Kim S, Fujiyama Y. Regulation of IL-11 expression in intestinal myofibroblasts: role of c-Jun AP-1- and MAPK-dependent pathways. Am J Physiol Gastrointest Liver Physiol 2003;285:G529-G538.
96. Casolaro V, et al. Posttranscriptional regulation of IL-13 in T cells: role of the RNA-binding protein HuR. J Allergy Clin Immunol 2008;121:853-859. e4.
97. Lee HH, et al. Tristetraprolin down-regulates IL-17 through mRNA destabilization. FEBS Lett 2012;586:41-46.
98. Di Marco S, et al. NF-kappa B-mediated MyoD decay during muscle wasting requires nitric oxide synthase mRNA stabilization, HuR protein, and nitric oxide release. Mol Cell Biol 2005;25:6533-6545.
99. Soderberg M, Raffalli-Mathieu F, Lang MA. Identification of a regulatory cis-element within the 3′-untranslated region of the murine inducible nitric oxide synthase (iNOS) mRNA; interaction with heterogeneous nuclear ribonucleoproteins I and L and role in the iNOS gene expression. Mol Immunol 2007;44:434-442.
100. Ostareck DH, Ostareck-Lederer A, Shatsky IN, Hentze MW. Lipoxygenase mRNA silencing in erythroid differentiation: the 3′UTR regulatory complex controls 60S ribosomal subunit joining. Cell 2001;104:281-290.
101. Ostareck DH, Ostareck-Lederer A, Wilm M, Thiele BJ, Mann M, Hentze MW. mRNA silencing in erythroid differentiation: hnRNP K and hnRNP E1 regulate 15-lipoxygenase translation from the 3′ end. Cell 1997;89:597-606.
102. Xia Z, Ghildyal N, Austen KF, Stevens RL. Post-transcriptional regulation of chymase expression in mast cells. A cytokine-dependent mechanism for controlling the expression of granule neutral proteases of hematopoietic cells. J Biol Chem 1996;271:8747-8753.
103. Huwiler A, el Akool S, Aschrafi A, Hamada FM, Pfeilschifter J, Eberhardt W. ATP potentiates interleukin-1 beta-induced MMP-9 expression in mesangial cells via recruitment of the ELAV protein HuR. J Biol Chem 2003;278:51758-51769.
104. Yu Q, Cok SJ, Zeng C, Morrison AR. Translational repression of human matrix metalloproteinases-13 by an alternatively spliced form of T-cell-restricted intracellular antigen-related protein (TIAR). J Biol Chem 2003;278:1579-1584.
105. Porter JF, Vavassori S, Covey LR. A polypyrimidine tract-binding protein-dependent pathway of mRNA stability initiates with CpG activation of primary B cells. J Immunol 2008;181:3336-3345.
106. Han J, Brown T, Beutler B. Endotoxin-responsive sequences control cachectin/tumor necrosis factor biosynthesis at the translational level. J Exp Med 1990;171:465-475.
107. Stoecklin G, Lu M, Rattenbacher B, Moroni C. A constitutive decay element promotes tumor necrosis factor alpha mRNA degradation via an AU-rich element-independent pathway. Mol Cell Biol 2003;23:3506-3515.
108. Yu C, York B, Wang S, Feng Q, Xu J, O'Malley BW. An essential function of the SRC-3 coactivator in suppression of cytokine mRNA translation and inflammatory response. Mol Cell 2007;25:765-778.
109. Croft D, McIntyre P, Wibulswas A, Kramer I. Sustained elevated levels of VCAM-1 in cultured fibroblast-like synoviocytes can be achieved by TNF-alpha in combination with either IL-4 or IL-13 through increased mRNA stability. Am J Pathol 1999;154:1149-1158.
110. Coles LS, et al. A multi-protein complex containing cold shock domain (Y-box) and polypyrimidine tract binding proteins forms on the vascular endothelial growth factor mRNA. Potential role in mRNA stabilization. Eur J Biochem 2004;271:648-660.
111. Dibbens JA, Miller DL, Damert A, Risau W, Vadas MA, Goodall GJ. Hypoxic regulation of vascular endothelial growth factor mRNA stability requires the cooperation of multiple RNA elements. Mol Biol Cell 1999;10:907-919.
112. Levy NS, Chung S, Furneaux H, Levy AP. Hypoxic stabilization of vascular endothelial growth factor mRNA by the RNA-binding protein HuR. J Biol Chem 1998;273:6417-6423.
113. Ray PS, Fox PL. A post-transcriptional pathway represses monocyte VEGF-A expression and angiogenic activity. EMBO J 2007;26:3360-3372.
114. Ray PS, Jia J, Yao P, Majumder M, Hatzoglou M, Fox PL. A stress-responsive RNA switch regulates VEGFA expression. Nature 2009;457:915-919.
115. Carballo E, Gilkeson GS, Blackshear PJ. Bone marrow transplantation reproduces the tristetraprolin-deficiency syndrome in recombination activating gene-2 (-/-) mice. Evidence that monocyte/macrophage progenitors may be responsible for TNFalpha overproduction. J Clin Invest 1997;100:986-995.
116. Taylor GA, et al. A pathogenetic role for TNF alpha in the syndrome of cachexia, arthritis, and autoimmunity resulting from tristetraprolin (TTP) deficiency. Immunity 1996;4:445-454.
117. Carballo E, Blackshear PJ. Roles of tumor necrosis factor-alpha receptor subtypes in the pathogenesis of the tristetraprolin-deficiency syndrome. Blood 2001;98:2389-2395.
118. Varnum BC, Ma QF, Chi TH, Fletcher B, Herschman HR. The TIS11 primary response gene is a member of a gene family that encodes proteins with a highly conserved sequence containing an unusual Cys-His repeat. Mol Cell Biol 1991;11:1754-1758.
119. Lai WS, Carballo E, Thorn JM, Kennington EA, Blackshear PJ. Interactions of CCCH zinc finger proteins with mRNA. Binding of tristetraprolin-related zinc finger proteins to Au-rich elements and destabilization of mRNA. J Biol Chem 2000;275:17827-17837.
120. Stoecklin G, Stoeckle P, Lu M, Muehlemann O, Moroni C. Cellular mutants define a common mRNA degradation pathway targeting cytokine AU-rich elements. RNA 2001;7:1578-1588.
121. Stumpo DJ, et al. Chorioallantoic fusion defects and embryonic lethality resulting from disruption of Zfp36L1, a gene encoding a CCCH tandem zinc finger protein of the Tristetraprolin family. Mol Cell Biol 2004;24:6445-6455.
122. Stumpo DJ, et al. Targeted disruption of Zfp36 l2, encoding a CCCH tandem zinc finger RNA-binding protein, results in defective hematopoiesis. Blood 2009;114:2401-2410.
123. Ramos SB, et al. The CCCH tandem zinc-finger protein Zfp36 l2 is crucial for female fertility and early embryonic development. Development 2004;131:4883-4893.
124. Brewer G, An A. + U-rich element RNA-binding factor regulates c-myc mRNA stability in vitro. Mol Cell Biol 1991;11:2460-2466.
125. Wagner BJ, DeMaria CT, Sun Y, Wilson GM, Brewer G. Structure and genomic organization of the human AUF1 gene: alternative pre-mRNA splicing generates four protein isoforms. Genomics 1998;48:195-202.
126. Sarkar S, Sinsimer KS, Foster RL, Brewer G, Pestka S. AUF1 isoform-specific regulation of anti-inflammatory IL10 expression in monocytes. J Interferon Cytokine Res 2008;28:679-691.
127. Sadri N, Lu JY, Badura ML, Schneider RJ. AUF1 is involved in splenic follicular B cell maintenance. BMC Immunol 2010;11:1.
128. Sadri N, Schneider RJ. Auf1/Hnrnpd-deficient mice develop pruritic inflammatory skin disease. J Invest Dermatol 2009;129:657-670.
129. Moraes KC, Quaresma AJ, Maehnss K, Kobarg J. Identification and characterization of proteins that selectively interact with isoforms of the mRNA binding protein AUF1 (hnRNP D). Biol Chem 2003;384:25-37.
130. Knapinska AM, et al. Chaperone Hsp27 modulates AUF1 proteolysis and AU-rich element-mediated mRNA degradation. Mol Cell Biol 2011;31:1419-1431.
131. Laroia G, Schneider RJ. Alternate exon insertion controls selective ubiquitination and degradation of different AUF1 protein isoforms. Nucleic Acids Res 2002;30:3052-3058.
132. Lu JY, Bergman N, Sadri N, Schneider RJ. Assembly of AUF1 with eIF4G-poly(A) binding protein complex suggests a translation function in AU-rich mRNA decay. RNA 2006;12:883-893.
133. Shen ZJ, Esnault S, Malter JS. The peptidyl-prolyl isomerase Pin1 regulates the stability of granulocyte-macrophage colony-stimulating factor mRNA in activated eosinophils. Nat Immunol 2005;6:1280-1287.
134. Srikantan S, Gorospe M. HuR function in disease. Front Biosci 2012;17:189-205.
135. Mukherjee N, et al. Integrative regulatory mapping indicates that the RNA-binding protein HuR couples pre-mRNA processing and mRNA stability. Mol Cell 2011;43:327-339.
136. Dixon DA, et al. Altered expression of the mRNA stability factor HuR promotes cyclooxygenase-2 expression in colon cancer cells. J Clin Invest. 2001;108:1657-1665.
137. Nabors LB, Gillespie GY, Harkins L, King PH. HuR, a RNA stability factor, is expressed in malignant brain tumors and binds to adenine- and uridine-rich elements within the 3′ untranslated regions of cytokine and angiogenic factor mRNAs. Cancer Res 2001;61:2154-2161.
138. Sung SC, et al. 7-Ketocholesterol upregulates interleukin-6 via mechanisms that are distinct from those of tumor necrosis factor-alpha, in vascular smooth muscle cells. J Vasc Res 2009;46:36-44.
139. Jacob CO, Tashman NB. Disruption in the AU motif of the mouse TNF-alpha 3′ UTR correlates with reduced TNF production by macrophages in vitro. Nucleic Acids Res 1993;21:2761-2766.
140. Jacob CO, McDevitt HO. Tumour necrosis factor-alpha in murine autoimmune 'lupus' nephritis. Nature 1988;331:356-358.
141. Jacob CO, Hwang F, Lewis GD, Stall AM. Tumor necrosis factor alpha in murine systemic lupus erythematosus disease models: implications for genetic predisposition and immune regulation. Cytokine 1991;3:551-561.
142. Gordon C, Ranges GE, Greenspan JS, Wofsy D. Chronic therapy with recombinant tumor necrosis factor-alpha in autoimmune NZB/NZW F1 mice. Clin Immunol Immunopathol 1989;52:421-434.
143. Katsanou V, et al. The RNA-binding protein Elavl1/HuR is essential for placental branching morphogenesis and embryonic development. Mol Cell Biol 2009;29:2762-2776.
144. Papadaki O, Milatos S, Grammenoudi S, Mukherjee N, Keene JD, Kontoyiannis DL. Control of thymic T cell maturation, deletion and egress by the RNA-binding protein HuR. J Immunol 2009;182:6779-6788.
145. Yiakouvaki A, Dimitriou M, Karakasiliotis I, Eftychi C, Theocharis S, Kontoyiannis DL. Myeloid cell expression of the RNA-binding protein HuR protects mice from pathologic inflammation and colorectal carcinogenesis. J Clin Invest 2012;122:48-61.
146. Anderson P. Post-transcriptional control of cytokine production. Nat Immunol 2008;9:353-359.
147. Schott J, Stoecklin G. Networks controlling mRNA decay in the immune system. Wiley Interdiscip Rev RNA 2010;1:432-456.
148. Hau HH, Walsh RJ, Ogilvie RL, Williams DA, Reilly CS, Bohjanen PR. Tristetraprolin recruits functional mRNA decay complexes to ARE sequences. J Cell Biochem 2007;100:1477-1492.
149. Lykke-Andersen J, Wagner E. Recruitment and activation of mRNA decay enzymes by two ARE-mediated decay activation domains in the proteins TTP and BRF-1. Genes Dev 2005;19:351-361.
150. Sandler H, Stoecklin G. Control of mRNA decay by phosphorylation of tristetraprolin. Biochem Soc Trans 2008;36:491-496.
151. Chou CF, et al. Tethering KSRP, a decay-promoting AU-rich element-binding protein, to mRNAs elicits mRNA decay. Mol Cell Biol 2006;26:3695-3706.
152. Chen CY, Del Gatto-Konczak F, Wu Z, Karin M. Stabilization of interleukin-2 mRNA by the c-Jun NH2-terminal kinase pathway. Science 1998;280:1945-1949.
153. Capowski EE, Esnault S, Bhattacharya S, Malter JS. Y box-binding factor promotes eosinophil survival by stabilizing granulocyte-macrophage colony-stimulating factor mRNA. J Immunol 2001;167:5970-5976.
154. Rattenbacher B, et al. Analysis of CUGBP1 targets identifies GU-repeat sequences that mediate rapid mRNA decay. Mol Cell Biol 2010;30:3970-3980.
155. Moraes KC, Wilusz CJ, Wilusz J. CUG-BP binds to RNA substrates and recruits PARN deadenylase. RNA 2006;12:1084-1091.
156. Gurish MF, Austen KF. Developmental origin and functional specialization of mast cell subsets. Immunity 2012;37:25-33.
157. Mullen TE, Marzluff WF. Degradation of histone mRNA requires oligouridylation followed by decapping and simultaneous degradation of the mRNA both 5′ to 3′ and 3′ to 5′. Genes Dev 2008;22:50-65.
158. Xu J, et al. Structural study of MCPIP1 N-terminal conserved domain reveals a PIN-like RNase. Nucleic Acids Res 2012;40:6957-6965.
159. Nicholson P, Yepiskoposyan H, Metze S. Zamudio Orozco R, Kleinschmidt N, Muhlemann O. Nonsense-mediated mRNA decay in human cells: mechanistic insights, functions beyond quality control and the double-life of NMD factors. Cell Mol Life Sci 2010;67:677-700.
160. Rebbapragada I, Lykke-Andersen J. Execution of nonsense-mediated mRNA decay: what defines a substrate? Curr Opin Cell Biol 2009;21:394-402.
161. Mendell JT, Sharifi NA, Meyers JL, Martinez-Murillo F, Dietz HC. Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise. Nat Genet 2004;36:1073-1078.
162. Le Hir H, Gatfield D, Izaurralde E, Moore MJ. The exon-exon junction complex provides a binding platform for factors involved in mRNA export and nonsense-mediated mRNA decay. EMBO J 2001;20:4987.
163. Maquat LE, Tarn WY, Isken O. The pioneer round of translation: features and functions. Cell 2010;142:368-374.
164. Eberle AB, Stalder L, Mathys H, Orozco RZ, Muhlemann O. Posttranscriptional gene regulation by spatial rearrangement of the 3′ untranslated region. PLoS Biol 2008;6:e92.
165. Ivanov PV, Gehring NH, Kunz JB, Hentze MW, Kulozik AE. Interactions between UPF1, eRFs, PABP and the exon junction complex suggest an integrated model for mammalian NMD pathways. EMBO J 2008;27:736-747.
166. Singh G, Rebbapragada I, Lykke-Andersen J. A competition between stimulators and antagonists of Upf complex recruitment governs human nonsense-mediated mRNA decay. PLoS Biol 2008;6:e111.
167. Eberle AB, Lykke-Andersen S, Muhlemann O, Jensen TH. SMG6 promotes endonucleolytic cleavage of nonsense mRNA in human cells. Nat Struct Mol Biol 2009;16:49-55.
168. Lykke-Andersen J. Identification of a human decapping complex associated with hUpf proteins in nonsense-mediated decay. Mol Cell Biol 2002;22:8114-8121.
169. Li S, Wilkinson MF. Nonsense surveillance in lymphocytes? Immunity 1998;8:135-141.
170. Baumann B, Potash MJ, Kohler G. Consequences of frameshift mutations at the immunoglobulin heavy chain locus of the mouse. EMBO J 1985;4:351-359.
171. Jack HM, Berg J, Wabl M. Translation affects immunoglobulin mRNA stability. Eur J Immunol 1989;19:843-847.
172. Connor A, Wiersma E, Shulman MJ. On the linkage between RNA processing and RNA translatability. J Biol Chem 1994;269:25178-25184.
173. Lozano F, Maertzdorf B, Pannell R, Milstein C. Low cytoplasmic mRNA levels of immunoglobulin kappa light chain genes containing nonsense codons correlate with inefficient splicing. EMBO J 1994;13:4617-4622.
174. Aoufouchi S, Yelamos J, Milstein C. Nonsense mutations inhibit RNA splicing in a cell-free system: recognition of mutant codon is independent of protein synthesis. Cell 1996;85:415-422.
175. Carter MS, Li S, Wilkinson MF. A splicing-dependent regulatory mechanism that detects translation signals. EMBO J 1996;15:5965-5975.
176. Carter MS, et al. A regulatory mechanism that detects premature nonsense codons in T-cell receptor transcripts in vivo is reversed by protein synthesis inhibitors in vitro. J Biol Chem 1995;270:28995-29003.
177. Chemin G, et al. Multiple RNA surveillance mechanisms cooperate to reduce the amount of nonfunctional Ig kappa transcripts. J Immunol 2010;184:5009-5017.
178. Tinguely A, et al. Cross talk between immunoglobulin heavy-chain transcription and RNA surveillance during B cell development. Mol Cell Biol 2012;32:107-117.
179. Wang J, Vock VM, Li S, Olivas OR, Wilkinson MF. A quality control pathway that down-regulates aberrant T-cell receptor (TCR) transcripts by a mechanism requiring UPF2 and translation. J Biol Chem 2002;277:18489-18493.
180. Apcher S, et al. Major source of antigenic peptides for the MHC class I pathway is produced during the pioneer round of mRNA translation. Proc Natl Acad Sci USA 2011;108:11572-11577.
181. Gracias DT, Katsikis PD. MicroRNAs: key components of immune regulation. Adv Exp Med Biol 2012;780:15-26.
182. O'Connell RM, Rao DS, Baltimore D. microRNA regulation of inflammatory responses. Annu Rev Immunol 2012;30:295-312.
183. Koralov SB, et al. Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage. Cell 2008;132:860-874.
184. Fedeli M, et al. Dicer-dependent microRNA pathway controls invariant NKT cell development. J Immunol 2009;183:2506-2512.
185. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005;120:15-20.
186. Asirvatham AJ, Gregorie CJ, Hu Z, Magner WJ, Tomasi TB. MicroRNA targets in immune genes and the Dicer/Argonaute and ARE machinery components. Mol Immunol 2008;45:1995-2006.
187. Zhou R, Gong AY, Eischeid AN, Chen XM. miR-27b targets KSRP to coordinate TLR4-mediated epithelial defense against Cryptosporidium parvum infection. PLoS Pathog 2012;8:e1002702.
188. Ruggiero T, et al. LPS induces KH-type splicing regulatory protein-dependent processing of microRNA-155 precursors in macrophages. FASEB J 2009;23:2898-2908.
189. Trabucchi M, et al. The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs. Nature 2009;459:1010-1014.
190. Lebedeva S, et al. Transcriptome-wide analysis of regulatory interactions of the RNA-binding protein HuR. Mol Cell 2011;43:340-352.
191. Abdelmohsen K, Tominaga-Yamanaka K, Srikantan S, Yoon JH, Kang MJ, Gorospe M. RNA-binding protein AUF1 represses Dicer expression. Nucleic Acids Res 2012;40:11531-11544.
192. Jing Q, et al. Involvement of microRNA in AU-rich element-mediated mRNA instability. Cell 2005;120:623-634.
193. Helfer S, Schott J, Stoecklin G, Forstemann K. AU-rich element-mediated mRNA decay can occur independently of the miRNA machinery in mouse embryonic fibroblasts and Drosophila S2-cells. PLoS ONE 2012;7:e28907.
194. Kim HH, Kuwano Y, Srikantan S, Lee EK, Martindale JL, Gorospe M. HuR recruits let-7/RISC to repress c-Myc expression. Genes Dev 2009;23:1743-1748.
195. Bhattacharyya SN, Habermacher R, Martine U, Closs EI, Filipowicz W. Relief of microRNA-mediated translational repression in human cells subjected to stress. Cell 2006;125:1111-1124.
196. Vasudevan S, Steitz JA. AU-rich-element-mediated upregulation of translation by FXR1 and Argonaute 2. Cell 2007;128:1105-1118.
197. Vasudevan S, Tong Y, Steitz JA. Switching from repression to activation: microRNAs can up-regulate translation. Science 2007;318:1931-1934.
198. Holcik M, Sonenberg N. Translational control in stress and apoptosis. Nat Rev Mol Cell Biol 2005;6:318-327.
199. Pestova TV, et al. Molecular mechanisms of translation initiation in eukaryotes. Proc Natl Acad Sci USA 2001;98:7029-7036.
200. Thomson AW, Turnquist HR, Raimondi G. Immunoregulatory functions of mTOR inhibition. Nat Rev Immunol 2009;9:324-337.
201. Cok SJ, Acton SJ, Sexton AE, Morrison AR. Identification of RNA-binding proteins in RAW 264.7 cells that recognize a lipopolysaccharide-responsive element in the 3-untranslated region of the murine cyclooxygenase-2 mRNA. J Biol Chem 2004;279:8196-8205.
202. Mazan-Mamczarz K, Lal A, Martindale JL, Kawai T, Gorospe M. Translational repression by RNA-binding protein TIAR. Mol Cell Biol 2006;26:2716-2727.
203. Tong X, Van Dross RT, Abu-Yousif A, Morrison AR, Pelling JC. Apigenin prevents UVB-induced cyclooxygenase 2 expression: coupled mRNA stabilization and translational inhibition. Mol Cell Biol 2007;27:283-296.
204. Ivanov P, Kedersha N, Anderson P. Stress puts TIA on TOP. Genes Dev 2011;25:2119-2124.
205. Yamasaki S, Stoecklin G, Kedersha N, Simarro M, Anderson P. T-cell intracellular antigen-1 (TIA-1)-induced translational silencing promotes the decay of selected mRNAs. J Biol Chem 2007;282:30070-30077.
206. Phillips K, Kedersha N, Shen L, Blackshear PJ, Anderson P. Arthritis suppressor genes TIA-1 and TTP dampen the expression of tumor necrosis factor alpha, cyclooxygenase 2, and inflammatory arthritis. Proc Natl Acad Sci USA 2004;101:2011-2016.
207. Scheu S, Stetson DB, Reinhardt RL, Leber JH, Mohrs M, Locksley RM. Activation of the integrated stress response during T helper cell differentiation. Nat Immunol 2006;7:644-651.
208. Glasmacher E, et al. Roquin binds inducible costimulator mRNA and effectors of mRNA decay to induce microRNA-independent post-transcriptional repression. Nat Immunol 2010;11:725-733.
209. Athanasopoulos V, et al. The ROQUIN family of proteins localizes to stress granules via the ROQ domain and binds target mRNAs. FEBS J 2010;277:2109-2127.
210. Sampath P, Mazumder B, Seshadri V, Fox PL. Transcript-selective translational silencing by gamma interferon is directed by a novel structural element in the ceruloplasmin mRNA 3′ untranslated region. Mol Cell Biol 2003;23:1509-1519.
211. Muhl H, Pfeilschifter J. Anti-inflammatory properties of pro-inflammatory interferon-gamma. Int Immunopharmacol 2003;3:1247-1255.
212. Vyas K, et al. Genome-wide polysome profiling reveals an inflammation-responsive posttranscriptional operon in gamma interferon-activated monocytes. Mol Cell Biol 2009;29:458-470.
213. Mukhopadhyay R, Jia J, Arif A, Ray PS, Fox PL. The GAIT system: a gatekeeper of inflammatory gene expression. Trends Biochem Sci 2009;34:324-331.
214. Mazumder B, Sampath P, Seshadri V, Maitra RK, DiCorleto PE, Fox PL. Regulated release of L13a from the 60S ribosomal subunit as a mechanism of transcript-specific translational control. Cell 2003;115:187-198.
215. Sampath P, et al. Noncanonical function of glutamyl-prolyl-tRNA synthetase: gene-specific silencing of translation. Cell 2004;119:195-208.
216. Kapasi P, et al. L13a blocks 48S assembly: role of a general initiation factor in mRNA-specific translational control. Mol Cell 2007;25:113-126.
217. Mazumder B, Seshadri V, Imataka H, Sonenberg N, Fox PL. Translational silencing of ceruloplasmin requires the essential elements of mRNA circularization: poly(A) tail, poly(A)-binding protein, and eukaryotic translation initiation factor 4G. Mol Cell Biol 2001;21:6440-6449.
218. Citores MJ, et al. The dinucleotide repeat polymorphism in the 3′UTR of the CD154 gene has a functional role on protein expression and is associated with systemic lupus erythematosus. Ann Rheum Dis 2004;63:310-317.
219. Glass CK, Ogawa S. Combinatorial roles of nuclear receptors in inflammation and immunity. Nat Rev Immunol 2006;6:44-55.
220. Rapoport SM, Schewe T. The maturational breakdown of mitochondria in reticulocytes. Biochim Biophys Acta 1986;864:471-495.
221. Straus DS, Glass CK. Cyclopentenone prostaglandins: new insights on biological activities and cellular targets. Med Res Rev 2001;21:185-210.
222. Straus DS, et al. 15-deoxy-delta 12, 14-prostaglandin J2 inhibits multiple steps in the NF-kappa B signaling pathway. Proc Natl Acad Sci USA 2000;97:4844-4849.
223. Straus DS, Glass CK. Anti-inflammatory actions of PPAR ligands: new insights on cellular and molecular mechanisms. Trends Immunol 2007;28:551-558.
224. Kim WJ, Kim JH, Jang SK. Anti-inflammatory lipid mediator 15d-PGJ2 inhibits translation through inactivation of eIF4A. EMBO J 2007;26:5020-5032.
225. Hilliard A, et al. Translational regulation of autoimmune inflammation and lymphoma genesis by programmed cell death 4. J Immunol 2006;177:8095-8102.
226. Munn DH, Mellor AL. Indoleamine 2, 3 dioxygenase and metabolic control of immune responses. Trends Immunol 2012; doi: 10.1016/j.it.2012.10.001.
227. Katz JB, Muller AJ, Prendergast GC. Indoleamine 2, 3-dioxygenase in T-cell tolerance and tumoral immune escape. Immunol Rev 2008;222:206-221.
228. Mezrich JD, Fechner JH, Zhang X, Johnson BP, Burlingham WJ, Bradfield CA. An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells. J Immunol 2010;185:3190-3198.
229. Nguyen NT, et al. Aryl hydrocarbon receptor negatively regulates dendritic cell immunogenicity via a kynurenine-dependent mechanism. Proc Natl Acad Sci USA 2010;107:19961-19966.
230. Stockinger B, Hirota K, Duarte J, Veldhoen M. External influences on the immune system via activation of the aryl hydrocarbon receptor. Semin Immunol 2011;23:99-105.
231. Baird TD, Wek RC. Eukaryotic initiation factor 2 phosphorylation and translational control in metabolism. Adv Nutr 2012;3:307-321.
232. Dong J, Qiu H, Garcia-Barrio M, Anderson J, Hinnebusch AG. Uncharged tRNA activates GCN2 by displacing the protein kinase moiety from a bipartite tRNA-binding domain. Mol Cell 2000;6:269-279.
233. Munn DH, et al. GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2, 3-dioxygenase. Immunity 2005;22:633-642.
234. Sundrud MS, et al. Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response. Science 2009;324:1334-1338.
235. Keller TL, et al. Halofuginone and other febrifugine derivatives inhibit prolyl-tRNA synthetase. Nat Chem Biol 2012;8:311-317.
236. Fallarino F, et al. The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells. J Immunol 2006;176:6752-6761.
237. Sharma MD, et al. Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2, 3-dioxygenase. J Clin Invest 2007;117:2570-2582.
238. Cao W, et al. Toll-like receptor-mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI(3)K-mTOR-p70S6K pathway. Nat Immunol 2008;9:1157-1164.
239. Colina R, et al. Translational control of the innate immune response through IRF-7. Nature 2008;452:323-328.
240. Herdy B, et al. Translational control of the activation of transcription factor NF-kappaB and production of type I interferon by phosphorylation of the translation factor eIF4E. Nat Immunol 2012;13:543-550.
241. Joshi B, et al. Phosphorylation of eukaryotic protein synthesis initiation factor 4E at Ser-209. J Biol Chem 1995;270:14597-14603.
242. Furic L, et al. eIF4E phosphorylation promotes tumorigenesis and is associated with prostate cancer progression. Proc Natl Acad Sci USA 2010;107:14134-14139.
243. Silverman N, Maniatis T. NF-kappaB signaling pathways in mammalian and insect innate immunity. Genes Dev 2001;15:2321-2342.
244. Hoffmann A, Levchenko A, Scott ML, Baltimore D. The IkappaB-NF-kappaB signaling module: temporal control and selective gene activation. Science 2002;298:1241-1245.