Publication Date:
2015-01-03
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").〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451101/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451101/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- 1DP2GM110772-01/DP/NCCDPHP CDC HHS/ -- DP2 GM110772/GM/NIGMS NIH HHS/ -- GM37949/GM/NIGMS NIH HHS/ -- GM37951/GM/NIGMS NIH HHS/ -- P50 GM102706/GM/NIGMS NIH HHS/ -- R01 GM037949/GM/NIGMS NIH HHS/ -- R01 GM037951/GM/NIGMS NIH HHS/ -- U01 GM098254/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jan 2;347(6217):75-8. doi: 10.1126/science.1259724.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Utah, UT 84112, USA. ; Department of Biochemistry, Stanford University, Palo Alto, CA 94305, USA. ; Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA. Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA. ; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. ; Mass Spectrometry and Proteomics Core Facility, University of Utah, UT 84112, USA. ; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA. Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA. California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, CA 94158, USA. Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA. ; Department of Biochemistry, University of Utah, UT 84112, USA. Mass Spectrometry and Proteomics Core Facility, University of Utah, UT 84112, USA. ; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA. Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA. California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, CA 94158, USA. Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA. jonathan.weissman@ucsf.edu onn@stanford.edu adam.frost@ucsf.edu. ; Department of Biochemistry, Stanford University, Palo Alto, CA 94305, USA. jonathan.weissman@ucsf.edu onn@stanford.edu adam.frost@ucsf.edu. ; Department of Biochemistry, University of Utah, UT 84112, USA. Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. jonathan.weissman@ucsf.edu onn@stanford.edu adam.frost@ucsf.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25554787" target="_blank"〉PubMed〈/a〉
Keywords:
Cryoelectron Microscopy
;
Nucleic Acid Conformation
;
*Peptide Biosynthesis, Nucleic Acid-Independent
;
Protein Conformation
;
RNA, Messenger/metabolism
;
RNA, Transfer, Ala/chemistry/metabolism
;
RNA, Transfer, Thr/chemistry/metabolism
;
Ribosome Subunits, Large, Eukaryotic/chemistry/*metabolism/ultrastructure
;
Saccharomyces cerevisiae/genetics/*metabolism
;
Saccharomyces cerevisiae Proteins/*metabolism/ultrastructure
;
Ubiquitin-Protein Ligases/*metabolism/ultrastructure
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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