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Nat Commun. 2018 Jun 6;9(1):2197. doi: 10.1038/s41467-018-04564-3.

Vms1p is a release factor for the ribosome-associated quality control complex.

Author information

1
Howard Hughes Medical Institute, Chevy Chase, MD, 20815-6789, USA.
2
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA.
3
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, 94158, USA.
4
California Institute for Quantitative Biomedical Research, San Francisco, CA, 94158, USA.
5
Molecular Medicine Program, University of Utah, Salt Lake City, UT, 84112, USA.
6
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, 94158, USA.
7
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA. adam.frost@ucsf.edu.
8
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, 94158, USA. adam.frost@ucsf.edu.
9
California Institute for Quantitative Biomedical Research, San Francisco, CA, 94158, USA. adam.frost@ucsf.edu.
10
Chan Zuckerberg Biohub, San Francisco, CA, 94158, USA. adam.frost@ucsf.edu.
11
Howard Hughes Medical Institute, Chevy Chase, MD, 20815-6789, USA. rutter@biochem.utah.edu.
12
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA. rutter@biochem.utah.edu.

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.

PMID:
29875445
PMCID:
PMC5989216
DOI:
10.1038/s41467-018-04564-3
[Indexed for MEDLINE]
Free PMC Article

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