Rqc2p and 60S ribosomal subunits mediate mRNA-independent elongation of nascent chains

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• Alternative Title:
  Science
• Personal Author:
  Shen, Peter S. ; Park, Joseph ; Qin, Yidan ; Li, Xueming ; Parsawar, Krishna ; Larson, Matthew H. ; Cox, James ; Cheng, Yifan ; Lambowitz, Alan M. ; Weissman, Jonathan S. ; Brandman, Onn ; Frost, Adam
• Description:
  In Eukarya, stalled translation induces 40S dissociation and recruitment of the ribosome quality control complex (RQC) to the 60S subunit, which mediates nascent chain degradation. Here we report cryo-electron microscopy structures revealing that the RQC components Rqc2p (YPL009C/Tae2) and Ltn1p (YMR247C/Rkr1) bind to the 60S subunit at sites exposed after 40S dissociation, placing the Ltn1p RING (Really Interesting New Gene) domain near the exit channel and Rqc2p over the P-site transfer RNA (tRNA). We further demonstrate that Rqc2p recruits alanine- and threonine-charged tRNA to the A site and directs the elongation of nascent chains independently of mRNA or 40S subunits. Our work uncovers an unexpected mechanism of protein synthesis, in which a protein--not an mRNA--determines tRNA recruitment and the tagging of nascent chains with carboxy-terminal Ala and Thr extensions ("CAT tails").
• Subjects:
  Article Cryoelectron Microscopy Nucleic Acid Conformation Peptide Biosynthesis, Nucleic Acid-Independent Protein Conformation Ribosome Subunits, Large, Eukaryotic RNA, Messenger RNA, Transfer, Ala RNA, Transfer, Thr Saccharomyces Cerevisiae Saccharomyces Cerevisiae Proteins Ubiquitin-Protein Ligases

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• Source:
  Science. 347(6217):75-78.
• Document Type:
  Journal Article
• Funding:
  1DP2GM110772-01/DP/NCCDPHP CDC HHS/United States ; DP2 GM110772/GM/NIGMS NIH HHS/United States ; GM37949/GM/NIGMS NIH HHS/United States ; GM37951/GM/NIGMS NIH HHS/United States ; P50 GM102706/GM/NIGMS NIH HHS/United States ; R01 GM037949/GM/NIGMS NIH HHS/United States ; R01 GM037951/GM/NIGMS NIH HHS/United States ; U01 GM098254/GM/NIGMS NIH HHS/United States ; U01 GM098254/GM/NIGMS NIH HHS/United States ; Howard Hughes Medical Institute/United States
• Volume:
  347
• Issue:
  6217
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:33fb53acbf412f4d9d8bb63148a48f84abc1dfe9abd7d9b9e502510545a66fff
• Download URL:
  https://stacks.cdc.gov/view/cdc/31393/cdc_31393_DS1.pdf
• File Type:
  [PDF - 1.36 MB ]