Abstract

Eukaryotic cells employ the ribosome-associated quality control complex (RQC) to maintain homeostasis despite defects that cause ribosomes to stall. The RQC comprises the E3 ubiquitin ligase Ltn1p, the ATPase Cdc48p, Rqc1p, and Rqc2p. Upon ribosome stalling and splitting, the RQC assembles on the 60S species containing unreleased peptidyl-tRNA (60S:peptidyl–tRNA). Ltn1p and Rqc1p facilitate ubiquitination of the incomplete nascent chain, marking it for degradation. Rqc2p stabilizes Ltn1p on the 60S and recruits charged tRNAs to the 60S to catalyze elongation of the nascent protein with carboxy-terminal alanine and threonine extensions (CAT tails). By mobilizing the nascent chain, CAT tailing can expose lysine residues that are hidden in the exit tunnel, thereby supporting efficient ubiquitination. If the ubiquitin–proteasome system is overwhelmed or unavailable, CAT-tailed nascent chains can aggregate in the cytosol or within organelles like mitochondria. Here we identify Vms1p as a tRNA hydrolase that releases stalled polypeptides engaged by the RQC.

Details

Title
Vms1p is a release factor for the ribosome-associated quality control complex
Author
Olga Zurita Rendón 1 ; Fredrickson, Eric K 2 ; Howard, Conor J 3   VIAFID ORCID Logo  ; Jonathan Van Vranken 2 ; Fogarty, Sarah 1 ; Tolley, Neal D 4 ; Kalia, Raghav 5 ; Osuna, Beatriz A 6 ; Shen, Peter S 2   VIAFID ORCID Logo  ; Hill, Christopher P 2 ; Frost, Adam 7   VIAFID ORCID Logo  ; Rutter, Jared 1   VIAFID ORCID Logo 

 Howard Hughes Medical Institute, Chevy Chase, MD, USA; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA 
 Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA 
 Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA; California Institute for Quantitative Biomedical Research, San Francisco, CA, USA 
 Molecular Medicine Program, University of Utah, Salt Lake City, UT, USA 
 Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA; California Institute for Quantitative Biomedical Research, San Francisco, CA, USA 
 Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA 
 Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA; California Institute for Quantitative Biomedical Research, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA 
Pages
1-9
Publication year
2018
Publication date
Jun 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2051034362
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.