Year: 2018
Type: article
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.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Howard Hughes Medical Institute, American Heart Association, University of Utah, Searle Scholars Program, Nora Eccles Treadwell Foundation, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G340239964, Cancer Center Support Grant, G3484198465, G3646000930, An Interdisciplinary Approach to Stress-Induced Mitochondrial Quality Control, Mitochondrial carbohydrate metabolism and the etiology of diabetic cardiomyopathy., G6601455508, Toward Atomic Resolution of Membranes and Membrane-Associated Machines, G781637850, G9000046377, G9000059365, G9000166915, G990796368
OpenAlex ID: W2949928712