Journal Article

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

Rutter, Jared, Fogarty, Sarah, Shen, Peter S., Zurita Rendón, Olga, Tolley, Neal D., Howard, Conor J., Kalia, Raghav, Frost, Adam, Fredrickson, Eric K., Van Vranken, Jonathan, Osuna, Beatriz A., Hill, Christopher P.

2018

Overview

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. The ribosome-associated quality control complex (RQC) functions to disassemble stalled ribosomes. Here the authors find that the tRNA hydrolase Vms1 is involved in the release of nascent peptide from stalled ribosomes.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 101/28 / 14 / 42/70 / 45/88 / 631/45/474/1768 / 631/80/642/333 / 82/29 / 82/80 / 96/31 / 96/35 / Adenosine triphosphatase / Alanine / Amino Acid Sequence / Carrier Proteins - genetics / Carrier Proteins - metabolism / Chain mobility / Chains / Cytosol / Elongation / Homeostasis / Humanities and Social Sciences / Hydrolase / Lysine / Mitochondria / multidisciplinary / Multiprotein Complexes - genetics / Multiprotein Complexes - metabolism / Organelles / Peptides - genetics / Peptides - metabolism / Polypeptides / Proteasomes / Protein Binding / Protein Biosynthesis - genetics / Proteins / Quality Control / Ribosome Subunits, Large, Eukaryotic - genetics / Ribosome Subunits, Large, Eukaryotic - metabolism / Ribosomes / RNA, Transfer, Amino Acyl - genetics / RNA, Transfer, Amino Acyl - metabolism / RNA-Binding Proteins - genetics / RNA-Binding Proteins - metabolism / Saccharomyces cerevisiae - genetics / Saccharomyces cerevisiae - metabolism / Saccharomyces cerevisiae Proteins - genetics / Saccharomyces cerevisiae Proteins - metabolism / Science / Science (multidisciplinary) / Sequence Homology, Amino Acid / Stalling / Threonine / tRNA / Ubiquitin / Ubiquitin-protein ligase / Ubiquitin-Protein Ligases - genetics / Ubiquitin-Protein Ligases - metabolism / Ubiquitination / Valosin Containing Protein - genetics / Valosin Containing Protein - metabolism