Cells of all organisms survey problems during translation elongation, which may happen as a consequence of mRNA aberrations, inefficient decoding, or other sources. In eukaryotes, ribosome-associated quality control (RQC) senses elongation-stalled ribosomes and promotes dissociation of ribosomal subunits. This so-called ribosomal rescue releases the mRNA for degradation and allows 40S subunits to be recycled for new rounds of translation. However, the nascent polypeptide chains remain linked to tRNA and associated with the rescued 60S subunits. As a final critical step in this pathway, the Ltn1/Listerin E3 ligase subunit of the RQC complex (RQCc) ubiquitylates the nascent chain, which promotes clearance of the 60S subunit while simultaneously marking the nascent chain for elimination. Here we review the ribosomal stalling and rescue steps upstream of the RQCc, where one witnesses intersection with cellular machineries implicated in translation elongation, translation termination, ribosomal subunit recycling, and mRNA quality control. We emphasize both recent progress and future directions in this area, as well as examples linking ribosomal rescue with the production of Ltn1-RQCc substrates.


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Literature Cited

  1. Adams DR, Ron D, Kiely PA. 2011. RACK1, a multifaceted scaffolding protein: structure and function. Cell Commun. Signal. 9:22 [Google Scholar]
  2. Arakawa S, Yunoki K, Izawa T, Tamura Y, Nishikawa S, Endo T. 2016. Quality control of nonstop membrane proteins at the ER membrane and in the cytosol. Sci. Rep. 2:30795 [Google Scholar]
  3. Arthur L, Pavlovic-Djuranovic S, Smith-Koutmou K, Green R, Szczesny P, Djuranovic S. 2015. Translational control by lysine-encoding A-rich sequences. Sci. Adv. 1:e1500154 [Google Scholar]
  4. Artieri CG, Fraser HB. 2014. Accounting for biases in riboprofiling data indicates a major role for proline in stalling translation. Genome Res 24:2011–21 [Google Scholar]
  5. Bartholomaus A, Del Campo C, Ignatova Z. 2016. Mapping the non-standardized biases of ribosome profiling. Biol. Chem. 397:23–35 [Google Scholar]
  6. Becker T, Armache JP, Jarasch A, Anger AM, Villa E. et al. 2011. Structure of the no-go mRNA decay complex Dom34-Hbs1 bound to a stalled 80S ribosome. Nat. Struct. Mol. Biol. 18:715–20 [Google Scholar]
  7. Bengtson MH, Joazeiro CA. 2010. Role of a ribosome-associated E3 ubiquitin ligase in protein quality control. Nature 467:470–73 [Google Scholar]
  8. Bostrom K, Wettesten M, Boren J, Bondjers G, Wiklund O, Olofsson SO. 1986. Pulse-chase studies of the synthesis and intracellular transport of apolipoprotein B-100 in Hep G2 cells. J. Biol. Chem. 261:13800–6 [Google Scholar]
  9. Brandman O, Hegde RS. 2016. Ribosome-associated protein quality control. Nat. Struct. Mol. Biol. 23:7–15 [Google Scholar]
  10. Brandman O, Stewart-Ornstein J, Wong D, Larson A, Williams CC. et al. 2012. A ribosome-bound quality control complex triggers degradation of nascent peptides and signals translation stress. Cell 151:1042–54 [Google Scholar]
  11. Brar GA. 2016. Beyond the triplet code: Context cues transform translation. Cell 167:1681–92 [Google Scholar]
  12. Braun MA, Costa PJ, Crisucci EM, Arndt KM. 2007. Identification of Rkr1, a nuclear RING domain protein with functional connections to chromatin modification in Saccharomyces cerevisiae. Mol. Cell. Biol. 27:2800–11 [Google Scholar]
  13. Brown CE, Sachs AB. 1998. Poly(A) tail length control in Saccharomyces cerevisiae occurs by message-specific deadenylation. Mol. Cell. Biol. 18:6548–59 [Google Scholar]
  14. Charneski CA, Hurst LD. 2013. Positively charged residues are the major determinants of ribosomal velocity. PLOS Biol 11:e1001508 [Google Scholar]
  15. Chen L, Muhlrad D, Hauryliuk V, Cheng Z, Lim MK. et al. 2010. Structure of the Dom34-Hbs1 complex and implications for no-go decay. Nat. Struct. Mol. Biol. 17:1233–40 [Google Scholar]
  16. Chiabudini M, Tais A, Zhang Y, Hayashi S, Wolfle T. et al. 2014. Release factor eRF3 mediates premature translation termination on polylysine-stalled ribosomes in Saccharomyces cerevisiae. Mol. Cell. Biol. 34:4062–76 [Google Scholar]
  17. Choe YJ, Park SH, Hassemer T, Korner R, Vincenz-Donnelly L. et al. 2016. Failure of RQC machinery causes protein aggregation and proteotoxic stress. Nature 531:191–95 [Google Scholar]
  18. Chu J, Hong NA, Masuda CA, Jenkins BV, Nelms KA. et al. 2009. A mouse forward genetics screen identifies LISTERIN as an E3 ubiquitin ligase involved in neurodegeneration. PNAS 106:2097–103 [Google Scholar]
  19. Collart MA. 2016. The Ccr4-Not complex is a key regulator of eukaryotic gene expression. Wiley Interdiscip. Rev. RNA 7:438–54 [Google Scholar]
  20. Comyn SA, Chan GT, Mayor T. 2014. False start: cotranslational protein ubiquitination and cytosolic protein quality control. J. Proteom. 100:92–101 [Google Scholar]
  21. Dacheux E, Firczuk H, McCarthy JE. 2015. Rate control in yeast protein synthesis at the population and single-cell levels. Biochem. Soc. Trans. 43:1266–70 [Google Scholar]
  22. Defenouillère Q, Yao Y, Mouaikel J, Namane A, Galopier A. et al. 2013. Cdc48-associated complex bound to 60S particles is required for the clearance of aberrant translation products. PNAS 110:5046–51 [Google Scholar]
  23. Defenouillère Q, Zhang E, Namane A, Mouaikel J, Jacquier A, Fromont-Racine M. 2016. Rqc1 and Ltn1 prevent C-terminal alanine-threonine tail (CAT-tail)-induced protein aggregation by efficient recruitment of Cdc48 on stalled 60S subunits. J. Biol. Chem. 291:12245–53 [Google Scholar]
  24. Deshaies RJ, Joazeiro CA. 2009. RING domain E3 ubiquitin ligases. Annu. Rev. Biochem. 78:399–434 [Google Scholar]
  25. Dever TE, Green R. 2012. The elongation, termination, and recycling phases of translation in eukaryotes. Cold Spring Harb. Perspect. Biol. 4:a013706 [Google Scholar]
  26. Dever TE, Kinzy TG, Pavitt GD. 2016. Mechanism and regulation of protein synthesis in Saccharomyces cerevisiae. Genetics 203:65–107 [Google Scholar]
  27. Dimitrova LN, Kuroha K, Tatematsu T, Inada T. 2009. Nascent peptide-dependent translation arrest leads to Not4p-mediated protein degradation by the proteasome. J. Biol. Chem. 284:10343–52 [Google Scholar]
  28. Doamekpor SK, Lee JW, Hepowit NL, Wu C, Charenton C. et al. 2016. Structure and function of the yeast listerin (Ltn1) conserved N-terminal domain in binding to stalled 60S ribosomal subunits. PNAS 113:E4151–60 [Google Scholar]
  29. Doerfel LK, Wohlgemuth I, Kothe C, Peske F, Urlaub H, Rodnina MV. 2013. EF-P is essential for rapid synthesis of proteins containing consecutive proline residues. Science 339:85–88 [Google Scholar]
  30. Doma MK, Parker R. 2006. Endonucleolytic cleavage of eukaryotic mRNAs with stalls in translation elongation. Nature 440:561–64 [Google Scholar]
  31. Duttler S, Pechmann S, Frydman J. 2013. Principles of cotranslational ubiquitination and quality control at the ribosome. Mol. Cell 50:379–93 [Google Scholar]
  32. Edenberg ER, Downey M, Toczyski D. 2014. Polymerase stalling during replication, transcription and translation. Curr. Biol. 24:R445–52 [Google Scholar]
  33. Fang P, Spevak CC, Wu C, Sachs MS. 2004. A nascent polypeptide domain that can regulate translation elongation. PNAS 101:4059–64 [Google Scholar]
  34. Fredrickson EK, Gardner RG. 2012. Selective destruction of abnormal proteins by ubiquitin-mediated protein quality control degradation. Semin. Cell Dev. Biol. 23:530–37 [Google Scholar]
  35. Frischmeyer PA, van Hoof A, O'Donnell K, Guerrerio AL, Parker R, Dietz HC. 2002. An mRNA surveillance mechanism that eliminates transcripts lacking termination codons. Science 295:2258–61 [Google Scholar]
  36. Gagnon MG, Seetharaman SV, Bulkley D, Steitz TA. 2012. Structural basis for the rescue of stalled ribosomes: structure of YaeJ bound to the ribosome. Science 335:1370–72 [Google Scholar]
  37. Gallo S, Manfrini N. 2015. Working hard at the nexus between cell signaling and the ribosomal machinery: an insight into the roles of RACK1 in translational regulation. Translation 3:e1120382 [Google Scholar]
  38. Gamble CE, Brule CE, Dean KM, Fields S, Grayhack EJ. 2016. Adjacent codons act in concert to modulate translation efficiency in yeast. Cell 166:679–90 [Google Scholar]
  39. Gamerdinger M. 2016. Protein quality control at the ribosome: focus on RAC, NAC and RQC. Essays Biochem 60:203–12 [Google Scholar]
  40. Gardin J, Yeasmin R, Yurovsky A, Cai Y, Skiena S, Futcher B. 2014. Measurement of average decoding rates of the 61 sense codons in vivo. eLife 3:e03735 [Google Scholar]
  41. Gerashchenko MV, Gladyshev VN. 2014. Translation inhibitors cause abnormalities in ribosome profiling experiments. Nucleic Acids Res 42:e134 [Google Scholar]
  42. Gerbasi VR, Weaver CM, Hill S, Friedman DB, Link AJ. 2004. Yeast Asc1p and mammalian RACK1 are functionally orthologous core 40S ribosomal proteins that repress gene expression. Mol. Cell. Biol. 24:8276–87 [Google Scholar]
  43. Ghaemmaghami S, Huh WK, Bower K, Howson RW, Belle A. et al. 2003. Global analysis of protein expression in yeast. Nature 425:737–41 [Google Scholar]
  44. Gloge F, Becker AH, Kramer G, Bukau B. 2014. Co-translational mechanisms of protein maturation. Curr. Opin. Struct. Biol. 24:24–33 [Google Scholar]
  45. Graille M, Seraphin B. 2012. Surveillance pathways rescuing eukaryotic ribosomes lost in translation. Nat. Rev. Mol. Cell Biol. 13:727–35 [Google Scholar]
  46. Gutierrez E, Shin BS, Woolstenhulme CJ, Kim JR, Saini P. et al. 2013. eIF5A promotes translation of polyproline motifs. Mol. Cell 51:35–45 [Google Scholar]
  47. Guydosh NR, Green R. 2014. Dom34 rescues ribosomes in 3′ untranslated regions. Cell 156:950–62 [Google Scholar]
  48. Guydosh NR, Green R. 2017. Translation of poly(A) tails leads to precise mRNA cleavage. RNA 23:749–61 [Google Scholar]
  49. Halic M, Becker T, Pool MR, Spahn CM, Grassucci RA. et al. 2004. Structure of the signal recognition particle interacting with the elongation-arrested ribosome. Nature 427:808–14 [Google Scholar]
  50. Halter D, Collart MA, Panasenko OO. 2014. The Not4 E3 ligase and Caf1/Ccr4 deadenylase play distinct roles in protein quality control. PLOS ONE 9:e86218 [Google Scholar]
  51. Harper JW, Bennett EJ. 2016. Proteome complexity and the forces that drive proteome imbalance. Nature 537:328–38 [Google Scholar]
  52. Higgins R, Gendron JM, Rising L, Mak R, Webb K. et al. 2015. The unfolded protein response triggers site-specific regulatory ubiquitylation of 40S ribosomal proteins. Mol. Cell 59:35–49 [Google Scholar]
  53. Hilal T, Spahn CM. 2015. Ribosome rescue and protein quality control in concert. Mol. Cell 57:389–90 [Google Scholar]
  54. Hilal T, Yamamoto H, Loerke J, Burger J, Mielke T, Spahn CM. 2016. Structural insights into ribosomal rescue by Dom34 and Hbs1 at near-atomic resolution. Nat. Commun. 7:13521 [Google Scholar]
  55. Hussmann JA, Patchett S, Johnson A, Sawyer S, Press WH. 2015. Understanding biases in ribosome profiling experiments reveals signatures of translation dynamics in yeast. PLOS Genet 11:e1005732 [Google Scholar]
  56. Huter P, Muller C, Beckert B, Arenz S, Berninghausen O. et al. 2017. Structural basis for ArfA-RF2-mediated translation termination on mRNAs lacking stop codons. Nature 541:546–49 [Google Scholar]
  57. Ikeuchi K, Inada T. 2016. Ribosome-associated Asc1/RACK1 is required for endonucleolytic cleavage induced by stalled ribosome at the 3′ end of nonstop mRNA. Sci. Rep. 6:28234 [Google Scholar]
  58. Inada T. 2017. The ribosome as a platform for mRNA and nascent polypeptide quality control. Trends Biochem. Sci. 42:5–15 [Google Scholar]
  59. Ingolia NT. 2016. Ribosome footprint profiling of translation throughout the genome. Cell 165:22–33 [Google Scholar]
  60. 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]
  61. Ishimura R, Nagy G, Dotu I, Zhou H, Yang XL. et al. 2014. Ribosome stalling induced by mutation of a CNS-specific tRNA causes neurodegeneration. Science 345:455–59 [Google Scholar]
  62. Isken O, Maquat LE. 2007. Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function. Genes Dev 21:1833–56 [Google Scholar]
  63. Ito K, Chiba S. 2013. Arrest peptides: cis-acting modulators of translation. Annu. Rev. Biochem. 82:171–202 [Google Scholar]
  64. Ito-Harashima S, Kuroha K, Tatematsu T, Inada T. 2007. Translation of the poly(A) tail plays crucial roles in nonstop mRNA surveillance via translation repression and protein destabilization by proteasome in yeast. Genes Dev 21:519–24 [Google Scholar]
  65. Izawa T, Tsuboi T, Kuroha K, Inada T, Nishikawa S, Endo T. 2012. Roles of dom34:hbs1 in nonstop protein clearance from translocators for normal organelle protein influx. Cell Rep 2:447–53 [Google Scholar]
  66. Juszkiewicz S, Hegde RS. 2017. Initiation of quality control during poly(A) translation requires site-specific ribosome ubiquitination. Mol. Cell 65:743–50 [Google Scholar]
  67. Keiler KC. 2015. Mechanisms of ribosome rescue in bacteria. Nat. Rev. Microbiol. 13:285–97 [Google Scholar]
  68. Koch HG, Moser M, Muller M. 2003. Signal recognition particle–dependent protein targeting, universal to all kingdoms of life. Rev. Physiol. Biochem. Pharmacol. 146:55–94 [Google Scholar]
  69. Kuroha K, Akamatsu M, Dimitrova L, Ito T, Kato Y. et al. 2010. Receptor for activated C kinase 1 stimulates nascent polypeptide–dependent translation arrest. EMBO Rep 11:956–61 [Google Scholar]
  70. Lareau LF, Hite DH, Hogan GJ, Brown PO. 2014. Distinct stages of the translation elongation cycle revealed by sequencing ribosome-protected mRNA fragments. eLife 3:e01257 [Google Scholar]
  71. Letzring DP, Wolf AS, Brule CE, Grayhack EJ. 2013. Translation of CGA codon repeats in yeast involves quality control components and ribosomal protein L1. RNA 19:1208–17 [Google Scholar]
  72. Li JJ, Xie D. 2015. RACK1, a versatile hub in cancer. Oncogene 34:1890–98 [Google Scholar]
  73. Liu B, Han Y, Qian SB. 2013. Cotranslational response to proteotoxic stress by elongation pausing of ribosomes. Mol. Cell 49:453–63 [Google Scholar]
  74. Lu J, Deutsch C. 2008. Electrostatics in the ribosomal tunnel modulate chain elongation rates. J. Mol. Biol. 384:73–86 [Google Scholar]
  75. Lykke-Andersen J, Bennett EJ. 2014. Protecting the proteome: eukaryotic cotranslational quality control pathways. J. Cell Biol. 204:467–76 [Google Scholar]
  76. Lyumkis D, Oliveira dos Passos D, Tahara EB, Webb K, Bennett EJ. et al. 2014. Structural basis for translational surveillance by the large ribosomal subunit–associated protein quality control complex. PNAS 111:15981–86 [Google Scholar]
  77. Ma C, Kurita D, Li N, Chen Y, Himeno H, Gao N. 2017. Mechanistic insights into the alternative translation termination by ArfA and RF2. Nature 541:550–53 [Google Scholar]
  78. Martens AT, Taylor J, Hilser VJ. 2015. Ribosome A and P sites revealed by length analysis of ribosome profiling data. Nucleic Acids Res 43:3680–87 [Google Scholar]
  79. Matsuda R, Ikeuchi K, Nomura S, Inada T. 2014. Protein quality control systems associated with no-go and nonstop mRNA surveillance in yeast. Genes Cells 19:1–12 [Google Scholar]
  80. Meaux S, Van Hoof A. 2006. Yeast transcripts cleaved by an internal ribozyme provide new insight into the role of the cap and poly(A) tail in translation and mRNA decay. RNA 12:1323–37 [Google Scholar]
  81. Moore SD, Sauer RT. 2007. The tmRNA system for translational surveillance and ribosome rescue. Annu. Rev. Biochem. 76:101–24 [Google Scholar]
  82. Munroe D, Jacobson A. 1990. mRNA poly(A) tail, a 3′ enhancer of translational initiation. Mol. Cell. Biol. 10:3441–55 [Google Scholar]
  83. Muto H, Ito K. 2008. Peptidyl-prolyl-tRNA at the ribosomal P-site reacts poorly with puromycin. Biochem. Biophys. Res. Commun. 366:1043–47 [Google Scholar]
  84. Nedialkova DD, Leidel SA. 2015. Optimization of codon translation rates via tRNA modifications maintains proteome integrity. Cell 161:1606–18 [Google Scholar]
  85. Neubauer C, Gillet R, Kelley AC, Ramakrishnan V. 2012. Decoding in the absence of a codon by tmRNA and SmpB in the ribosome. Science 335:1366–69 [Google Scholar]
  86. Ozsolak F, Kapranov P, Foissac S, Kim SW, Fishilevich E. et al. 2010. Comprehensive polyadenylation site maps in yeast and human reveal pervasive alternative polyadenylation. Cell 143:1018–29 [Google Scholar]
  87. Pavlov MY, Watts RE, Tan Z, Cornish VW, Ehrenberg M, Forster AC. 2009. Slow peptide bond formation by proline and other N-alkylamino acids in translation. PNAS 106:50–54 [Google Scholar]
  88. Pelechano V, Wei W, Steinmetz LM. 2015. Widespread co-translational RNA decay reveals ribosome dynamics. Cell 161:1400–12 [Google Scholar]
  89. Pisareva VP, Skabkin MA, Hellen CU, Pestova TV, Pisarev AV. 2011. Dissociation by Pelota, Hbs1 and ABCE1 of mammalian vacant 80S ribosomes and stalled elongation complexes. EMBO J 30:1804–17 [Google Scholar]
  90. Pop C, Rouskin S, Ingolia NT, Han L, Phizicky EM. et al. 2014. Causal signals between codon bias, mRNA structure, and the efficiency of translation and elongation. Mol. Syst. Biol. 10:770 [Google Scholar]
  91. Preis A, Heuer A, Barrio-Garcia C, Hauser A, Eyler DE. et al. 2014. Cryoelectron microscopic structures of eukaryotic translation termination complexes containing eRF1-eRF3 or eRF1-ABCE1. Cell Rep 8:59–65 [Google Scholar]
  92. Preissler S, Deuerling E. 2012. Ribosome-associated chaperones as key players in proteostasis. Trends Biochem. Sci. 37:274–83 [Google Scholar]
  93. Preissler S, Reuther J, Koch M, Scior A, Bruderek M. et al. 2015. Not4-dependent translational repression is important for cellular protein homeostasis in yeast. EMBO J 34:1905–24 [Google Scholar]
  94. Requiao RD, de Souza HJ, Rossetto S, Domitrovic T, Palhano FL. 2016. Increased ribosome density associated to positively charged residues is evident in ribosome profiling experiments performed in the absence of translation inhibitors. RNA Biol 13:561–68 [Google Scholar]
  95. Richter JD, Coller J. 2015. Pausing on polyribosomes: Make way for elongation in translational control. Cell 163:292–300 [Google Scholar]
  96. Sabi R, Tuller T. 2015. A comparative genomics study on the effect of individual amino acids on ribosome stalling. BMC Genom 16:Suppl. 105 [Google Scholar]
  97. Saito K, Horikawa W, Ito K. 2015. Inhibiting K63 polyubiquitination abolishes no-go type stalled translation surveillance in Saccharomyces cerevisiae. PLOS Genet. 11:e1005197 [Google Scholar]
  98. Saito S, Hosoda N, Hoshino S. 2013. The Hbs1-Dom34 protein complex functions in non-stop mRNA decay in mammalian cells. J. Biol. Chem. 288:17832–43 [Google Scholar]
  99. Schmidt C, Kowalinski E, Shanmuganathan V, Defenouillère Q, Braunger K. et al. 2016. The cryo-EM structure of a ribosome-Ski2-Ski3-Ski8 helicase complex. Science 354:1431–33 [Google Scholar]
  100. Schubert U, Anton LC, Gibbs J, Norbury CC, Yewdell JW, Bennink JR. 2000. Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature 404:770–74 [Google Scholar]
  101. Shalgi R, Hurt JA, Krykbaeva I, Taipale M, Lindquist S, Burge CB. 2013. Widespread regulation of translation by elongation pausing in heat shock. Mol. Cell 49:439–52 [Google Scholar]
  102. Shao S, Brown A, Santhanam B, Hegde RS. 2015. Structure and assembly pathway of the ribosome quality control complex. Mol. Cell 57:433–44 [Google Scholar]
  103. Shao S, Hegde RS. 2014. Reconstitution of a minimal ribosome-associated ubiquitination pathway with purified factors. Mol. Cell 55:880–90 [Google Scholar]
  104. Shao S, Hegde RS. 2016. Target selection during protein quality control. Trends Biochem. Sci. 41:124–37 [Google Scholar]
  105. Shao S, von der Malsburg K, Hegde RS. 2013. Listerin-dependent nascent protein ubiquitination relies on ribosome subunit dissociation. Mol. Cell 50:637–48 [Google Scholar]
  106. Shcherbik N, Chernova TA, Chernoff YO, Pestov DG. 2016. Distinct types of translation termination generate substrates for ribosome-associated quality control. Nucleic Acids Res 44:6840–52 [Google Scholar]
  107. Shen PS, Park J, Qin Y, Li X, Parsawar K. et al. 2015. Rqc2p and 60S ribosomal subunits mediate mRNA-independent elongation of nascent chains. Science 347:75–78 [Google Scholar]
  108. Shoemaker CJ, Eyler DE, Green R. 2010. Dom34:Hbs1 promotes subunit dissociation and peptidyl-tRNA drop-off to initiate no-go decay. Science 330:369–72 [Google Scholar]
  109. Shoemaker CJ, Green R. 2011. Kinetic analysis reveals the ordered coupling of translation termination and ribosome recycling in yeast. PNAS 108:E1392–98 [Google Scholar]
  110. Shoemaker CJ, Green R. 2012. Translation drives mRNA quality control. Nat. Struct. Mol. Biol. 19:594–601 [Google Scholar]
  111. Simms CL, Zaher HS. 2016. Quality control of chemically damaged RNA. Cell. Mol. Life Sci. 73:3639–53 [Google Scholar]
  112. Sitron CS, Park JH, Brandman O. 2017. Asc1, Hel2, and Slh1 couple translation arrest to nascent chain degradation. RNA 23:798–810 [Google Scholar]
  113. Starosta AL, Lassak J, Jung K, Wilson DN. 2014. The bacterial translation stress response. FEMS Microbiol. Rev. 38:1172–201 [Google Scholar]
  114. Sundaramoorthy E, Leonard M, Mak R, Liao J, Fulzele A, Bennett EJ. 2017. ZNF598 and RACK1 regulate mammalian ribosome-associated quality control function by mediating regulatory 40S ribosomal ubiquitylation. Mol. Cell 65:751–60.e4 [Google Scholar]
  115. Taylor D, Unbehaun A, Li W, Das S, Lei J. et al. 2012. Cryo-EM structure of the mammalian eukaryotic release factor eRF1-eRF3-associated termination complex. PNAS 109:18413–18 [Google Scholar]
  116. Tsuboi T, Kuroha K, Kudo K, Makino S, Inoue E. et al. 2012. Dom34:hbs1 plays a general role in quality-control systems by dissociation of a stalled ribosome at the 3′ end of aberrant mRNA. Mol. Cell 46:518–29 [Google Scholar]
  117. van Hoof A, Frischmeyer PA, Dietz HC, Parker R. 2002. Exosome-mediated recognition and degradation of mRNAs lacking a termination codon. Science 295:2262–64 [Google Scholar]
  118. Verma R, Oania RS, Kolawa NJ, Deshaies RJ. 2013. Cdc48/p97 promotes degradation of aberrant nascent polypeptides bound to the ribosome. eLife 2:e00308 [Google Scholar]
  119. Voorhees RM, Ramakrishnan V. 2013. Structural basis of the translational elongation cycle. Annu. Rev. Biochem. 82:203–36 [Google Scholar]
  120. Wang F, Canadeo LA, Huibregtse JM. 2015. Ubiquitination of newly synthesized proteins at the ribosome. Biochimie 114:127–33 [Google Scholar]
  121. Wei J, Wu C, Sachs MS. 2012. The arginine attenuator peptide interferes with the ribosome peptidyl transferase center. Mol. Cell. Biol. 32:2396–406 [Google Scholar]
  122. Weinberg DE, Shah P, Eichhorn SW, Hussmann JA, Plotkin JB, Bartel DP. 2016. Improved ribosome-footprint and mRNA measurements provide insights into dynamics and regulation of yeast translation. Cell Rep 14:1787–99 [Google Scholar]
  123. Wilson DN, Arenz S, Beckmann R. 2016. Translation regulation via nascent polypeptide–mediated ribosome stalling. Curr. Opin. Struct. Biol. 37:123–33 [Google Scholar]
  124. Wilson MA, Meaux S, van Hoof A. 2007. A genomic screen in yeast reveals novel aspects of nonstop mRNA metabolism. Genetics 177:773–84 [Google Scholar]
  125. Wohlgemuth I, Brenner S, Beringer M, Rodnina MV. 2008. Modulation of the rate of peptidyl transfer on the ribosome by the nature of substrates. J. Biol. Chem. 283:32229–35 [Google Scholar]
  126. Wolf AS, Grayhack EJ. 2015. Asc1, homolog of human RACK1, prevents frameshifting in yeast by ribosomes stalled at CGA codon repeats. RNA 21:935–45 [Google Scholar]
  127. Woolstenhulme CJ, Guydosh NR, Green R, Buskirk AR. 2015. High-precision analysis of translational pausing by ribosome profiling in bacteria lacking EFP. Cell Rep 11:13–21 [Google Scholar]
  128. Yamamoto H, Qin Y, Achenbach J, Li C, Kijek J. et al. 2014. EF-G and EF4: translocation and back-translocation on the bacterial ribosome. Nat. Rev. Microbiol. 12:89–100 [Google Scholar]
  129. Yonashiro R, Tahara EB, Bengtson MH, Khokhrina M, Lorenz H. et al. 2016. The Rqc2/Tae2 subunit of the ribosome-associated quality control (RQC) complex marks ribosome-stalled nascent polypeptide chains for aggregation. eLife 5:e11794 [Google Scholar]
  130. Zeng F, Chen Y, Remis J, Shekhar M, Phillips JC. et al. 2017. Structural basis of co-translational quality control by ArfA and RF2 bound to ribosome. Nature 541:554–57 [Google Scholar]
  131. Zenklusen D, Larson DR, Singer RH. 2008. Single-RNA counting reveals alternative modes of gene expression in yeast. Nat. Struct. Mol. Biol. 15:1263–71 [Google Scholar]

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