1932

Abstract

The emergence of genome-wide analyses to interrogate cellular DNA, RNA, and protein content has revolutionized the study of control networks that mediate cellular homeostasis. mRNA translation represents the last step of genetic flow and primarily defines the proteome. Translational regulation is thus critical for gene expression, in particular under nutrient excess or deficiency. Until recently, it was unclear how the global effects of translational control are orchestrated by nutrient signaling pathways. An emerging concept of translational reprogramming addresses how to maintain the expression of specific proteins during nutrient stress by translation of selective mRNAs. In this review, we describe recent advances in our understanding of translational control principles; nutrient-sensing mechanisms; and their dysregulation in human diseases such as diabetes, cancer, and aging. The mechanistic understanding of translational regulation in response to different nutrient conditions may help identify potential dietary and therapeutic targets to improve human health.

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2020-08-21
2024-04-24
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Literature Cited

  1. 1. 
    Abu-Remaileh M, Wyant GA, Kim C, Laqtom NN, Abbasi M et al. 2017. Lysosomal metabolomics reveals V-ATPase- and mTOR-dependent regulation of amino acid efflux from lysosomes. Science 358:807–13
    [Google Scholar]
  2. 2. 
    Adams CM. 2007. Role of the transcription factor ATF4 in the anabolic actions of insulin and the anti-anabolic actions of glucocorticoids. J. Biol. Chem. 282:16744–53
    [Google Scholar]
  3. 3. 
    Alarcon CR, Goodarzi H, Lee H, Liu X, Tavazoie S, Tavazoie SF 2015. HNRNPA2B1 is a mediator of m6A-dependent nuclear RNA processing events. Cell 162:1299–308
    [Google Scholar]
  4. 4. 
    Arango D, Sturgill D, Alhusaini N, Dillman AA, Sweet TJ et al. 2018. Acetylation of cytidine in mRNA promotes translation efficiency. Cell 175:1872–86.e24
    [Google Scholar]
  5. 5. 
    Archer SK, Shirokikh NE, Beilharz TH, Preiss T 2016. Dynamics of ribosome scanning and recycling revealed by translation complex profiling. Nature 535:570–74
    [Google Scholar]
  6. 6. 
    Auxilien S, Guerineau V, Szweykowska-Kulinska Z, Golinelli-Pimpaneau B 2012. The human tRNA m5C methyltransferase Misu is multisite-specific. RNA Biol 9:1331–38
    [Google Scholar]
  7. 7. 
    Balch WE, Morimoto RI, Dillin A, Kelly JW 2008. Adapting proteostasis for disease intervention. Science 319:916–19
    [Google Scholar]
  8. 8. 
    Bandi HR, Ferrari S, Krieg J, Meyer HE, Thomas G 1993. Identification of 40 S ribosomal protein S6 phosphorylation sites in Swiss mouse 3T3 fibroblasts stimulated with serum. J. Biol. Chem. 268:4530–33
    [Google Scholar]
  9. 9. 
    Bar-Peled L, Chantranupong L, Cherniack AD, Chen WW, Ottina KA et al. 2013. A tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. Science 340:1100–6
    [Google Scholar]
  10. 10. 
    Bar-Peled L, Schweitzer LD, Zoncu R, Sabatini DM 2012. Ragulator is a GEF for the Rag GTPases that signal amino acid levels to mTORC1. Cell 150:1196–208
    [Google Scholar]
  11. 11. 
    Barbosa C, Peixeiro I, Romao L 2013. Gene expression regulation by upstream open reading frames and human disease. PLOS Genet 9:e1003529
    [Google Scholar]
  12. 12. 
    Bhat M, Robichaud N, Hulea L, Sonenberg N, Pelletier J, Topisirovic I 2015. Targeting the translation machinery in cancer. Nat. Rev. Drug Discov. 14:261–78
    [Google Scholar]
  13. 13. 
    Brar GA, Weissman JS. 2015. Ribosome profiling reveals the what, when, where and how of protein synthesis. Nat. Rev. Mol. Cell Biol. 16:651–64
    [Google Scholar]
  14. 14. 
    Brina D, Miluzio A, Ricciardi S, Clarke K, Davidsen PK et al. 2015. eIF6 coordinates insulin sensitivity and lipid metabolism by coupling translation to transcription. Nat. Commun. 6:8261
    [Google Scholar]
  15. 15. 
    Calvo SE, Pagliarini DJ, Mootha VK 2009. Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans. PNAS 106:7507–12
    [Google Scholar]
  16. 16. 
    Cattie DJ, Richardson CE, Reddy KC, Ness-Cohn EM, Droste R et al. 2016. Mutations in nonessential eIF3k and eIF3l genes confer lifespan extension and enhanced resistance to ER stress in Caenorhabditis elegans. . PLOS Genet 12:e1006326
    [Google Scholar]
  17. 17. 
    Cavener DR, Zhang PC, McGrath BC, Reinert J, Olsen DS et al. 2002. The GCN2 eIF2α kinase is required for adaptation to amino acid deprivation in mice. Mol. Cell. Biol. 22:6681–88
    [Google Scholar]
  18. 18. 
    Chan CT, Pang YL, Deng W, Babu IR, Dyavaiah M et al. 2012. Reprogramming of tRNA modifications controls the oxidative stress response by codon-biased translation of proteins. Nat. Commun. 3:937
    [Google Scholar]
  19. 19. 
    Chantranupong L, Scaria SM, Saxton RA, Gygi MP, Shen K et al. 2016. The CASTOR proteins are arginine sensors for the mTORC1 pathway. Cell 165:153–64
    [Google Scholar]
  20. 20. 
    Child SJ, Miller MK, Geballe AP 1999. Translational control by an upstream open reading frame in the HER-2/neu transcript. J. Biol. Chem. 274:24335–41
    [Google Scholar]
  21. 21. 
    Choe J, Lin S, Zhang W, Liu Q, Wang L et al. 2018. mRNA circularization by METTL3-eIF3h enhances translation and promotes oncogenesis. Nature 561:556–60
    [Google Scholar]
  22. 22. 
    Choi J, Ieong KW, Demirci H, Chen J, Petrov A et al. 2016. N6-Methyladenosine in mRNA disrupts tRNA selection and translation-elongation dynamics. Nat. Struct. Mol. Biol. 23:110–15
    [Google Scholar]
  23. 23. 
    Cole MD, Cowling VH. 2008. Transcription-independent functions of MYC: regulation of translation and DNA replication. Nat. Rev. Mol. Cell Biol. 9:810–15
    [Google Scholar]
  24. 24. 
    Coots RA, Liu XM, Mao Y, Dong L, Zhou J et al. 2017. m6A facilitates eIF4F-independent mRNA translation. Mol. Cell 68:504–14.e7
    [Google Scholar]
  25. 25. 
    Copeland PR, Donovan J. 2010. Threading the needle: getting selenocysteine into proteins. Antioxid. Redox Signal. 12:881–92
    [Google Scholar]
  26. 26. 
    Datta B, Ray MK, Chakrabarti D, Wylie DE, Gupta NK 1989. Glycosylation of eukaryotic peptide chain initiation factor 2 (eIF-2)-associated 67-kDa polypeptide (p67) and its possible role in the inhibition of eIF-2 kinase–catalyzed phosphorylation of the eIF-2α subunit. J. Biol. Chem. 264:20620–24
    [Google Scholar]
  27. 27. 
    Datta R, Choudhury P, Ghosh A, Datta B 2003. A glycosylation site, 60SGTS63, of p67 is required for its ability to regulate the phosphorylation and activity of eukaryotic initiation factor 2α. Biochemistry 42:5453–60
    [Google Scholar]
  28. 28. 
    Dennis MD, Schrufer TL, Bronson SK, Kimball SR, Jefferson LS 2011. Hyperglycemia-induced O-GlcNAcylation and truncation of 4E-BP1 protein in liver of a mouse model of type 1 diabetes. J. Biol. Chem. 286:34286–97
    [Google Scholar]
  29. 29. 
    Dever TE, Dinman JD, Green R 2018. Translation elongation and recoding in eukaryotes. Cold Spring Harb. Perspect. Biol. 10:a032649
    [Google Scholar]
  30. 30. 
    Dever TE, Green R. 2012. The elongation, termination, and recycling phases of translation in eukaryotes. Cold Spring Harb. Perspect. Biol. 4:a013706
    [Google Scholar]
  31. 31. 
    Dey S, Sayers CM, Verginadis II, Lehman SL, Cheng Y et al. 2015. ATF4-dependent induction of heme oxygenase 1 prevents anoikis and promotes metastasis. J. Clin. Investig. 125:2592–608
    [Google Scholar]
  32. 32. 
    Dierschke SK, Miller WP, Favate JS, Shah P, Imamura Kawasawa Y et al. 2019. O-GlcNAcylation alters the selection of mRNAs for translation and promotes 4E-BP1-dependent mitochondrial dysfunction in the retina. J. Biol. Chem. 294:5508–20
    [Google Scholar]
  33. 33. 
    Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM et al. 2012. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149:1060–72
    [Google Scholar]
  34. 34. 
    Dominissini D, Moshitch-Moshkovitz S, Schwartz S, Salmon-Divon M, Ungar L et al. 2012. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 485:201–6
    [Google Scholar]
  35. 35. 
    Donovan J, Copeland PR. 2012. Selenocysteine insertion sequence binding protein 2L is implicated as a novel post-transcriptional regulator of selenoprotein expression. PLOS ONE 7:e35581
    [Google Scholar]
  36. 36. 
    Dowling RJ, Topisirovic I, Alain T, Bidinosti M, Fonseca BD et al. 2010. mTORC1-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs. Science 328:1172–76
    [Google Scholar]
  37. 37. 
    Drummond DA, Wilke CO. 2009. The evolutionary consequences of erroneous protein synthesis. Nat. Rev. Genet. 10:715–24
    [Google Scholar]
  38. 38. 
    Edupuganti RR, Geiger S, Lindeboom RGH, Shi H, Hsu PJ et al. 2017. N6-Methyladenosine (m6A) recruits and repels proteins to regulate mRNA homeostasis. Nat. Struct. Mol. Biol. 24:870–78
    [Google Scholar]
  39. 39. 
    Efeyan A, Zoncu R, Sabatini DM 2011. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat. Rev. Mol. Cell Biol. 12:21–35
    [Google Scholar]
  40. 40. 
    Frankel LB. 2018. eIF5A mediates autophagy via translation of ATG3. Autophagy 14:1288–89
    [Google Scholar]
  41. 41. 
    Frye M, Harada BT, Behm M, He C 2018. RNA modifications modulate gene expression during development. Science 361:1346–49
    [Google Scholar]
  42. 42. 
    Fu Y, Dominissini D, Rechavi G, He C 2014. Gene expression regulation mediated through reversible m6A RNA methylation. Nat. Rev. Genet. 15:293–306
    [Google Scholar]
  43. 43. 
    Gameiro PA, Struhl K. 2018. Nutrient deprivation elicits a transcriptional and translational inflammatory response coupled to decreased protein synthesis. Cell Rep 24:1415–24
    [Google Scholar]
  44. 44. 
    Gao X, Wan J, Liu B, Ma M, Shen B, Qian SB 2015. Quantitative profiling of initiating ribosomes in vivo. Nat. Methods 12:147–53
    [Google Scholar]
  45. 45. 
    Gao X, Wan J, Qian SB 2016. Genome-wide profiling of alternative translation initiation sites. Methods Mol. Biol. 1358:303–16
    [Google Scholar]
  46. 46. 
    Garigan D, Hsu AL, Fraser AG, Kamath RS, Ahringer J, Kenyon C 2002. Genetic analysis of tissue aging in Caenorhabditis elegans: a role for heat-shock factor and bacterial proliferation. Genetics 161:1101–12
    [Google Scholar]
  47. 47. 
    Gonskikh Y, Polacek N. 2017. Alterations of the translation apparatus during aging and stress response. Mech. Ageing Dev. 168:30–36
    [Google Scholar]
  48. 48. 
    Gray NK, Wickens M. 1998. Control of translation initiation in animals. Annu. Rev. Cell Dev. Biol. 14:399–458
    [Google Scholar]
  49. 49. 
    Green DR, Galluzzi L, Kroemer G 2014. Cell biology. Metabolic control of cell death. Science 345:1250256
    [Google Scholar]
  50. 50. 
    Gu X, Orozco JM, Saxton RA, Condon KJ, Liu GY et al. 2017. SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway. Science 358:813–18
    [Google Scholar]
  51. 51. 
    Haghighat A, Mader S, Pause A, Sonenberg N 1995. Repression of cap-dependent translation by 4E-binding protein 1: competition with p220 for binding to eukaryotic initiation factor 4E. EMBO J 14:5701–9
    [Google Scholar]
  52. 52. 
    Han Y, Gao X, Liu B, Wan J, Zhang X, Qian SB 2014. Ribosome profiling reveals sequence-independent post-initiation pausing as a signature of translation. Cell Res 24:842–51
    [Google Scholar]
  53. 53. 
    Harper JW, Bennett EJ. 2016. Proteome complexity and the forces that drive proteome imbalance. Nature 537:328–38
    [Google Scholar]
  54. 54. 
    Hart GW. 2019. Nutrient regulation of signaling and transcription. J. Biol. Chem. 294:2211–31
    [Google Scholar]
  55. 55. 
    Hawkes WC, Alkan Z. 2010. Regulation of redox signaling by selenoproteins. Biol. Trace Elem. Res. 134:235–51
    [Google Scholar]
  56. 56. 
    He PC, He C. 2019. mRNA acetylation: a new addition to the epitranscriptome. Cell Res 29:91–92
    [Google Scholar]
  57. 57. 
    Hellen CU, Sarnow P. 2001. Internal ribosome entry sites in eukaryotic mRNA molecules. Genes Dev 15:1593–612
    [Google Scholar]
  58. 58. 
    Hinnebusch AG. 1997. Translational regulation of yeast GCN4. J. Biol. Chem. 272:21661–64
    [Google Scholar]
  59. 59. 
    Hinnebusch AG. 2014. The scanning mechanism of eukaryotic translation initiation. Annu. Rev. Biochem. 83:779–812
    [Google Scholar]
  60. 60. 
    Hinnebusch AG. 2017. Structural insights into the mechanism of scanning and start codon recognition in eukaryotic translation initiation. Trends Biochem. Sci. 42:589–611
    [Google Scholar]
  61. 61. 
    Ho JJD, Lee S. 2016. A cap for every occasion: alternative eIF4F complexes. Trends Biochem. Sci. 41:821–23
    [Google Scholar]
  62. 62. 
    Holcik M, Sonenberg N. 2005. Translational control in stress and apoptosis. Nat. Rev. Mol. Cell Biol. 6:318–27
    [Google Scholar]
  63. 63. 
    Howard MT, Carlson BA, Anderson CB, Hatfield DL 2013. Translational redefinition of UGA codons is regulated by selenium availability. J. Biol. Chem. 288:19401–13
    [Google Scholar]
  64. 64. 
    Hsieh AC, Liu Y, Edlind MP, Ingolia NT, Janes MR et al. 2012. The translational landscape of mTOR signalling steers cancer initiation and metastasis. Nature 485:55–61
    [Google Scholar]
  65. 65. 
    Hsu AL, Murphy CT, Kenyon C 2003. Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science 300:1142–45
    [Google Scholar]
  66. 66. 
    Ingolia NT, Ghaemmaghami S, Newman JR, Weissman JS 2009. Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling. Science 324:218–23
    [Google Scholar]
  67. 67. 
    Ingolia NT, Lareau LF, Weissman JS 2011. Ribosome profiling of mouse embryonic stem cells reveals the complexity and dynamics of mammalian proteomes. Cell 147:789–802
    [Google Scholar]
  68. 68. 
    Inoki K, Li Y, Zhu T, Wu J, Guan KL 2002. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat. Cell Biol. 4:648–57
    [Google Scholar]
  69. 69. 
    Iqbal N, Iqbal N. 2014. Human epidermal growth factor receptor 2 (HER2) in cancers: overexpression and therapeutic implications. Biochem. Mol. Biol. Int. 2014:852748
    [Google Scholar]
  70. 70. 
    Ivanov IP, Wei J, Caster SZ, Smith KM, Michel AM et al. 2017. Translation initiation from conserved non-AUG codons provides additional layers of regulation and coding capacity. mBio 8:e00844-17
    [Google Scholar]
  71. 71. 
    Jackson RJ, Hellen CU, Pestova TV 2010. The mechanism of eukaryotic translation initiation and principles of its regulation. Nat. Rev. Mol. Cell Biol. 11:113–27
    [Google Scholar]
  72. 72. 
    Jan CH, Williams CC, Weissman JS 2014. Principles of ER cotranslational translocation revealed by proximity-specific ribosome profiling. Science 346:1257521
    [Google Scholar]
  73. 73. 
    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]
  74. 74. 
    Jo S, Lockridge A, Alejandro EU 2019. eIF4G1 and carboxypeptidase E axis dysregulation in O-GlcNAc transferase–deficient pancreatic β-cells contributes to hyperproinsulinemia in mice. J. Biol. Chem. 294:13040–50
    [Google Scholar]
  75. 75. 
    Johnstone TG, Bazzini AA, Giraldez AJ 2016. Upstream ORFs are prevalent translational repressors in vertebrates. EMBO J 35:706–23
    [Google Scholar]
  76. 76. 
    Kearse MG, Wilusz JE. 2017. Non-AUG translation: a new start for protein synthesis in eukaryotes. Genes Dev 31:1717–31
    [Google Scholar]
  77. 77. 
    Kilberg MS, Pan YX, Chen H, Leung-Pineda V 2005. Nutritional control of gene expression: how mammalian cells respond to amino acid limitation. Annu. Rev. Nutr. 25:59–85
    [Google Scholar]
  78. 78. 
    Kim E, Goraksha-Hicks P, Li L, Neufeld TP, Guan KL 2008. Regulation of TORC1 by Rag GTPases in nutrient response. Nat. Cell Biol. 10:935–45
    [Google Scholar]
  79. 79. 
    Kim J, Guan KL. 2019. mTOR as a central hub of nutrient signalling and cell growth. Nat. Cell Biol. 21:63–71
    [Google Scholar]
  80. 80. 
    Kozak M. 1989. The scanning model for translation: an update. J. Cell Biol. 108:229–41
    [Google Scholar]
  81. 81. 
    Kracht MJ, van Lummel M, Nikolic T, Joosten AM, Laban S et al. 2017. Autoimmunity against a defective ribosomal insulin gene product in type 1 diabetes. Nat. Med. 23:501–7
    [Google Scholar]
  82. 82. 
    Krishnamoorthy T, Pavitt GD, Zhang F, Dever TE, Hinnebusch AG 2001. Tight binding of the phosphorylated alpha subunit of initiation factor 2 (eIF2α) to the regulatory subunits of guanine nucleotide exchange factor eIF2B is required for inhibition of translation initiation. Mol. Cell. Biol. 21:5018–30
    [Google Scholar]
  83. 83. 
    Lama L, Cobo J, Buenaventura D, Ryan K 2019. Small RNA-seq: the RNA 5′-end adapter ligation problem and how to circumvent it. J. Biol. Methods 6:e108
    [Google Scholar]
  84. 84. 
    Laplante M, Sabatini DM. 2012. mTOR signaling in growth control and disease. Cell 149:274–93
    [Google Scholar]
  85. 85. 
    Laxman S, Sutter BM, Wu X, Kumar S, Guo X et al. 2013. Sulfur amino acids regulate translational capacity and metabolic homeostasis through modulation of tRNA thiolation. Cell 154:416–29
    [Google Scholar]
  86. 86. 
    Lee AS, Kranzusch PJ, Doudna JA, Cate JH 2016. eIF3d is an mRNA cap-binding protein that is required for specialized translation initiation. Nature 536:96–99
    [Google Scholar]
  87. 87. 
    Lee S, Liu B, Lee S, Huang SX, Shen B, Qian SB 2012. Global mapping of translation initiation sites in mammalian cells at single-nucleotide resolution. PNAS 109:E2424–32
    [Google Scholar]
  88. 88. 
    Leib DE, Knight ZA. 2015. Re-examination of dietary amino acid sensing reveals a GCN2-independent mechanism. Cell Rep 13:1081–89
    [Google Scholar]
  89. 89. 
    Levine ZG, Walker S. 2016. The biochemistry of O-GlcNAc transferase: Which functions make it essential in mammalian cells. Annu. Rev. Biochem. 85:631–57
    [Google Scholar]
  90. 90. 
    Li X, Zhu Q, Shi X, Cheng Y, Li X et al. 2019. O-GlcNAcylation of core components of the translation initiation machinery regulates protein synthesis. PNAS 116:7857–66
    [Google Scholar]
  91. 91. 
    Liu B, Qian SB. 2014. Translational reprogramming in cellular stress response. Wiley Interdiscip. Rev. RNA 5:301–15
    [Google Scholar]
  92. 92. 
    Liu J, Yue Y, Han D, Wang X, Fu Y et al. 2014. A METTL3−METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat. Chem. Biol. 10:93–95
    [Google Scholar]
  93. 93. 
    Liu TY, Huang HH, Wheeler D, Xu Y, Wells JA et al. 2017. Time-resolved proteomics extends ribosome profiling-based measurements of protein synthesis dynamics. Cell Syst 4:636–44.e9
    [Google Scholar]
  94. 94. 
    Liu XM, Zhou J, Mao Y, Ji Q, Qian SB 2019. Programmable RNA N6-methyladenosine editing by CRISPR-Cas9 conjugates. Nat. Chem. Biol. 15:865–71
    [Google Scholar]
  95. 95. 
    Loayza-Puch F, Rooijers K, Buil LC, Zijlstra J, Oude Vrielink JF et al. 2016. Tumour-specific proline vulnerability uncovered by differential ribosome codon reading. Nature 530:490–94
    [Google Scholar]
  96. 96. 
    Lu PD, Harding HP, Ron D 2004. Translation reinitiation at alternative open reading frames regulates gene expression in an integrated stress response. J. Cell Biol. 167:27–33
    [Google Scholar]
  97. 97. 
    Ma J, Hart GW. 2014. O-GlcNAc profiling: from proteins to proteomes. Clin. Proteom. 11:8
    [Google Scholar]
  98. 98. 
    Ma XM, Blenis J. 2009. Molecular mechanisms of mTOR-mediated translational control. Nat. Rev. Mol. Cell Biol. 10:307–18
    [Google Scholar]
  99. 99. 
    Madeo F, Zimmermann A, Maiuri MC, Kroemer G 2015. Essential role for autophagy in life span extension. J. Clin. Investig. 125:85–93
    [Google Scholar]
  100. 100. 
    Mao Y, Dong L, Liu X-M, Guo J, Ma H et al. 2019. m6A in mRNA coding regions promotes translation via the RNA helicase−containing YTHDC2. Nat. Commun. 10:5532
    [Google Scholar]
  101. 101. 
    Markman B, Dienstmann R, Tabernero J 2010. Targeting the PI3K/Akt/mTOR pathway—beyond rapalogs. Oncotarget 1:530–43
    [Google Scholar]
  102. 102. 
    Martin-Marcos P, Zhou F, Karunasiri C, Zhang F, Dong J et al. 2017. eIF1A residues implicated in cancer stabilize translation preinitiation complexes and favor suboptimal initiation sites in yeast. eLife 6:e31250
    [Google Scholar]
  103. 103. 
    Mazor KM, Dong L, Mao Y, Swanda RV, Qian SB, Stipanuk MH 2018. Effects of single amino acid deficiency on mRNA translation are markedly different for methionine versus leucine. Sci. Rep. 8:8076
    [Google Scholar]
  104. 104. 
    McBean GJ, Flynn J. 2001. Molecular mechanisms of cystine transport. Biochem. Soc. Trans. 29:717–22
    [Google Scholar]
  105. 105. 
    Mehta A, Trotta CR, Peltz SW 2006. Derepression of the Her-2 uORF is mediated by a novel post-transcriptional control mechanism in cancer cells. Genes Dev 20:939–53
    [Google Scholar]
  106. 106. 
    Merrick WC. 2004. Cap-dependent and cap-independent translation in eukaryotic systems. Gene 332:1–11
    [Google Scholar]
  107. 107. 
    Meyer KD, Jaffrey SR. 2017. Rethinking m6A readers, writers, and erasers. Annu. Rev. Cell Dev. Biol. 33:319–42
    [Google Scholar]
  108. 108. 
    Meyer KD, Patil DP, Zhou J, Zinoviev A, Skabkin MA et al. 2015. 5′ UTR m6A promotes cap-independent translation. Cell 163:999–1010
    [Google Scholar]
  109. 109. 
    Meyer KD, Saletore Y, Zumbo P, Elemento O, Mason CE, Jaffrey SR 2012. Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons. Cell 149:1635–46
    [Google Scholar]
  110. 110. 
    Mobin MB, Gerstberger S, Teupser D, Campana B, Charisse K et al. 2016. The RNA-binding protein vigilin regulates VLDL secretion through modulation of Apob mRNA translation. Nat. Commun. 7:12848
    [Google Scholar]
  111. 111. 
    Moor AE, Golan M, Massasa EE, Lemze D, Weizman T et al. 2017. Global mRNA polarization regulates translation efficiency in the intestinal epithelium. Science 357:1299–303
    [Google Scholar]
  112. 112. 
    Morimoto RI. 1998. Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes Dev 12:3788–96
    [Google Scholar]
  113. 113. 
    Morley JF, Morimoto RI. 2004. Regulation of longevity in Caenorhabditis elegans by heat shock factor and molecular chaperones. Mol. Biol. Cell 15:657–64
    [Google Scholar]
  114. 114. 
    Nachtergaele S, He C. 2018. Chemical modifications in the life of an mRNA transcript. Annu. Rev. Genet. 52:349–72
    [Google Scholar]
  115. 115. 
    Nakamura S, Oba M, Suzuki M, Takahashi A, Yamamuro T et al. 2019. Suppression of autophagic activity by Rubicon is a signature of aging. Nat. Commun. 10:847
    [Google Scholar]
  116. 116. 
    Nedialkova DD, Leidel SA. 2015. Optimization of codon translation rates via tRNA modifications maintains proteome integrity. Cell 161:1606–18
    [Google Scholar]
  117. 117. 
    Netzer N, Goodenbour JM, David A, Dittmar KA, Jones RB et al. 2009. Innate immune and chemically triggered oxidative stress modifies translational fidelity. Nature 462:522–26
    [Google Scholar]
  118. 118. 
    Oh E, Becker AH, Sandikci A, Huber D, Chaba R et al. 2011. Selective ribosome profiling reveals the cotranslational chaperone action of trigger factor in vivo. Cell 147:1295–308
    [Google Scholar]
  119. 119. 
    Ohn T, Kedersha N, Hickman T, Tisdale S, Anderson P 2008. A functional RNAi screen links O-GlcNAc modification of ribosomal proteins to stress granule and processing body assembly. Nat. Cell Biol. 10:1224–31
    [Google Scholar]
  120. 120. 
    Palm W, Park Y, Wright K, Pavlova NN, Tuveson DA, Thompson CB 2015. The utilization of extracellular proteins as nutrients is suppressed by mTORC1. Cell 162:259–70
    [Google Scholar]
  121. 121. 
    Pelletier J, Graff J, Ruggero D, Sonenberg N 2015. Targeting the eIF4F translation initiation complex: a critical nexus for cancer development. Cancer Res 75:250–63
    [Google Scholar]
  122. 122. 
    Potter CJ, Pedraza LG, Xu T 2002. Akt regulates growth by directly phosphorylating Tsc2. Nat. Cell Biol. 4:658–65
    [Google Scholar]
  123. 123. 
    Rieckher M, Markaki M, Princz A, Schumacher B, Tavernarakis N 2018. Maintenance of proteostasis by P body–mediated regulation of eIF4E availability during aging in Caenorhabditis elegans. . Cell Rep 25:199–211.e6
    [Google Scholar]
  124. 124. 
    Rogers AN, Chen D, McColl G, Czerwieniec G, Felkey K et al. 2011. Life span extension via eIF4G inhibition is mediated by posttranscriptional remodeling of stress response gene expression in C. elegans. . Cell Metab 14:55–66
    [Google Scholar]
  125. 125. 
    Roundtree IA, Evans ME, Pan T, He C 2017. Dynamic RNA modifications in gene expression regulation. Cell 169:1187–200
    [Google Scholar]
  126. 126. 
    Ruggero D. 2013. Translational control in cancer etiology. Cold Spring Harb. Perspect. Biol. 5:a012336
    [Google Scholar]
  127. 127. 
    Saikia M, Krokowski D, Guan BJ, Ivanov P, Parisien M et al. 2012. Genome-wide identification and quantitative analysis of cleaved tRNA fragments induced by cellular stress. J. Biol. Chem. 287:42708–25
    [Google Scholar]
  128. 128. 
    Saikia M, Wang X, Mao Y, Wan J, Pan T, Qian SB 2016. Codon optimality controls differential mRNA translation during amino acid starvation. RNA 22:1719–27
    [Google Scholar]
  129. 129. 
    Sancak Y, Bar-Peled L, Zoncu R, Markhard AL, Nada S, Sabatini DM 2010. Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 141:290–303
    [Google Scholar]
  130. 130. 
    Sancak Y, Peterson TR, Shaul YD, Lindquist RA, Thoreen CC et al. 2008. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 320:1496–501
    [Google Scholar]
  131. 131. 
    Santos DA, Shi L, Tu BP, Weissman JS 2019. Cycloheximide can distort measurements of mRNA levels and translation efficiency. Nucleic Acids Res 47:4974–85
    [Google Scholar]
  132. 132. 
    Sato H, Tamba M, Ishii T, Bannai S 1999. Cloning and expression of a plasma membrane cystine/glutamate exchange transporter composed of two distinct proteins. J. Biol. Chem. 274:11455–58
    [Google Scholar]
  133. 133. 
    Schuster SL, Hsieh AC. 2019. The untranslated regions of mRNAs in cancer. Trends Cancer 5:245–62
    [Google Scholar]
  134. 134. 
    Schwanhäusser B, Busse D, Li N, Dittmar G, Schuchhardt J et al. 2011. Global quantification of mammalian gene expression control. Nature 473:337–42
    [Google Scholar]
  135. 135. 
    Sendoel A, Dunn JG, Rodriguez EH, Naik S, Gomez NC et al. 2017. Translation from unconventional 5′ start sites drives tumour initiation. Nature 541:494–99
    [Google Scholar]
  136. 136. 
    Sergiev PV, Aleksashin NA, Chugunova AA, Polikanov YS, Dontsova OA 2018. Structural and evolutionary insights into ribosomal RNA methylation. Nat. Chem. Biol. 14:226–35
    [Google Scholar]
  137. 137. 
    Seyedali A, Berry MJ. 2014. Nonsense-mediated decay factors are involved in the regulation of selenoprotein mRNA levels during selenium deficiency. RNA 20:1248–56
    [Google Scholar]
  138. 138. 
    Shaw RJ, Cantley LC. 2006. Ras, PI3K and mTOR signalling controls tumour cell growth. Nature 441:424–30
    [Google Scholar]
  139. 139. 
    Shendure J, Ji H. 2008. Next-generation DNA sequencing. Nat. Biotechnol. 26:1135–45
    [Google Scholar]
  140. 140. 
    Shi H, Wang X, Lu Z, Zhao BS, Ma H et al. 2017. YTHDF3 facilitates translation and decay of N6-methyladenosine-modified RNA. Cell Res 27:315–28
    [Google Scholar]
  141. 141. 
    Shi Z, Fujii K, Kovary KM, Genuth NR, Rost HL et al. 2017. Heterogeneous ribosomes preferentially translate distinct subpools of mRNAs genome-wide. Mol. Cell 67:71–83.e7
    [Google Scholar]
  142. 142. 
    Shiber A, Doring K, Friedrich U, Klann K, Merker D et al. 2018. Cotranslational assembly of protein complexes in eukaryotes revealed by ribosome profiling. Nature 561:268–72
    [Google Scholar]
  143. 143. 
    Shirokikh NE, Preiss T. 2018. Translation initiation by cap-dependent ribosome recruitment: recent insights and open questions. Wiley Interdiscip. Rev. RNA 9:e1473
    [Google Scholar]
  144. 144. 
    Silvera D, Arju R, Darvishian F, Levine PH, Zolfaghari L et al. 2009. Essential role for eIF4GI overexpression in the pathogenesis of inflammatory breast cancer. Nat. Cell Biol. 11:903–8
    [Google Scholar]
  145. 145. 
    Silvera D, Formenti SC, Schneider RJ 2010. Translational control in cancer. Nat. Rev. Cancer 10:254–66
    [Google Scholar]
  146. 146. 
    Skabkin MA, Skabkina OV, Hellen CU, Pestova TV 2013. Reinitiation and other unconventional posttermination events during eukaryotic translation. Mol. Cell 51:249–64
    [Google Scholar]
  147. 147. 
    Sokabe M, Fraser CS. 2017. A helicase-independent activity of eIF4A in promoting mRNA recruitment to the human ribosome. PNAS 114:6304–9
    [Google Scholar]
  148. 148. 
    Sonenberg N, Hinnebusch AG. 2007. New modes of translational control in development, behavior, and disease. Mol. Cell 28:721–29
    [Google Scholar]
  149. 149. 
    Sonenberg N, Hinnebusch AG. 2009. Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell 136:731–45
    [Google Scholar]
  150. 150. 
    Starck SR, Jiang V, Pavon-Eternod M, Prasad S, McCarthy B et al. 2012. Leucine-tRNA initiates at CUG start codons for protein synthesis and presentation by MHC class I. Science 336:1719–23
    [Google Scholar]
  151. 151. 
    Stipanuk MH, Dominy JE Jr, Lee JI, Coloso RM 2006. Mammalian cysteine metabolism: new insights into regulation of cysteine metabolism. J. Nutr 136:S1652–59
    [Google Scholar]
  152. 152. 
    Stockwell BR, Friedmann Angeli JP, Bayir H, Bush AI, Conrad M et al. 2017. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell 171:273–85
    [Google Scholar]
  153. 153. 
    Tang X, Keenan MM, Wu J, Lin CA, Dubois L et al. 2015. Comprehensive profiling of amino acid response uncovers unique methionine-deprived response dependent on intact creatine biosynthesis. PLOS Genet 11:e1005158
    [Google Scholar]
  154. 154. 
    Thompson DM, Lu C, Green PJ, Parker R 2008. tRNA cleavage is a conserved response to oxidative stress in eukaryotes. RNA 14:2095–103
    [Google Scholar]
  155. 155. 
    Thoreen CC, Chantranupong L, Keys HR, Wang T, Gray NS, Sabatini DM 2012. A unifying model for mTORC1-mediated regulation of mRNA translation. Nature 485:109–13
    [Google Scholar]
  156. 156. 
    Townsend DM, Tew KD, Tapiero H 2003. The importance of glutathione in human disease. Biomed. Pharmacother. 57:145–55
    [Google Scholar]
  157. 157. 
    Truitt ML, Ruggero D. 2016. New frontiers in translational control of the cancer genome. Nat. Rev. Cancer 16:288–304
    [Google Scholar]
  158. 158. 
    Vattem KM, Wek RC. 2004. Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cells. PNAS 101:11269–74
    [Google Scholar]
  159. 159. 
    Wang P, Doxtader KA, Nam Y 2016. Structural basis for cooperative function of Mettl3 and Mettl14 methyltransferases. Mol. Cell 63:306–17
    [Google Scholar]
  160. 160. 
    Wang X, Zhao BS, Roundtree IA, Lu Z, Han D et al. 2015. N6-Methyladenosine modulates messenger RNA translation efficiency. Cell 161:1388–99
    [Google Scholar]
  161. 161. 
    Webster GC, Webster SL. 1983. Decline in synthesis of elongation factor one (EF-1) precedes the decreased synthesis of total protein in aging Drosophila melanogaster. Mech. . Ageing Dev 22:121–28
    [Google Scholar]
  162. 162. 
    Williams CC, Jan CH, Weissman JS 2014. Targeting and plasticity of mitochondrial proteins revealed by proximity-specific ribosome profiling. Science 346:748–51
    [Google Scholar]
  163. 163. 
    Wolfson RL, Chantranupong L, Saxton RA, Shen K, Scaria SM et al. 2016. Sestrin2 is a leucine sensor for the mTORC1 pathway. Science 351:43–48
    [Google Scholar]
  164. 164. 
    Wu C. 1995. Heat shock transcription factors: structure and regulation. Annu. Rev. Cell Dev. Biol. 11:441–69
    [Google Scholar]
  165. 165. 
    Xue S, Barna M. 2012. Specialized ribosomes: a new frontier in gene regulation and organismal biology. Nat. Rev. Mol. Cell Biol. 13:355–69
    [Google Scholar]
  166. 166. 
    Yang Y, Fan X, Mao M, Song X, Wu P et al. 2017. Extensive translation of circular RNAs driven by N6-methyladenosine. Cell Res 27:626–41
    [Google Scholar]
  167. 167. 
    Yewdell JW, Dersh D, Fahraeus R 2019. Peptide channeling: the key to MHC class I immunosurveillance. Trends Cell Biol 29:929–39
    [Google Scholar]
  168. 168. 
    Young DJ, Guydosh NR, Zhang F, Hinnebusch AG, Green R 2015. Rli1/ABCE1 recycles terminating ribosomes and controls translation reinitiation in 3′UTRs in vivo. Cell 162:872–84
    [Google Scholar]
  169. 169. 
    Yourik P, Aitken CE, Zhou F, Gupta N, Hinnebusch AG, Lorsch JR 2017. Yeast eIF4A enhances recruitment of mRNAs regardless of their structural complexity. eLife 6:e31476
    [Google Scholar]
  170. 170. 
    Yueh A, Schneider RJ. 2000. Translation by ribosome shunting on adenovirus and hsp70 mRNAs facilitated by complementarity to 18S rRNA. Genes Dev 14:414–21
    [Google Scholar]
  171. 171. 
    Zachara N, Akimoto Y, Hart GW 2015. The O-GlcNAc modification. Essentials of Glycobiology A Varki, RD Cummings, JD Esko, P Stanley, GW Hart et al.239–51 Cold Spring Harbor, NY: Cold Spring Harb. Lab. Press. , 3rd ed..
    [Google Scholar]
  172. 172. 
    Zeidan Q, Wang Z, De Maio A, Hart GW 2010. O-GlcNAc cycling enzymes associate with the translational machinery and modify core ribosomal proteins. Mol. Biol. Cell 21:1922–36
    [Google Scholar]
  173. 173. 
    Zhang X, Shu XE, Qian SB 2018. O-GlcNAc modification of eIF4GI acts as a translational switch in heat shock response. Nat. Chem. Biol. 14:909–16
    [Google Scholar]
  174. 174. 
    Zheng G, Dahl JA, Niu Y, Fedorcsak P, Huang C-M et al. 2013. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol. Cell 49:18–29
    [Google Scholar]
  175. 175. 
    Zhou J, Wan J, Gao X, Zhang X, Jaffrey SR, Qian S-B 2015. Dynamic m6A mRNA methylation directs translational control of heat shock response. Nature 526:591–94
    [Google Scholar]
  176. 176. 
    Zhou J, Wan J, Shu XE, Mao Y, Liu XM et al. 2018. N6-Methyladenosine guides mRNA alternative translation during integrated stress response. Mol. Cell 69:636–47.e7
    [Google Scholar]
  177. 177. 
    Zhu Y, Liu TW, Cecioni S, Eskandari R, Zandberg WF, Vocadlo DJ 2015. O-GlcNAc occurs cotranslationally to stabilize nascent polypeptide chains. Nat. Chem. Biol. 11:319–25
    [Google Scholar]
  178. 178. 
    Zidek LM, Ackermann T, Hartleben G, Eichwald S, Kortman G et al. 2015. Deficiency in mTORC1-controlled C/EBPβ-mRNA translation improves metabolic health in mice. EMBO Rep 16:1022–36
    [Google Scholar]
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