Vms1p is a release factor for the Ribosome-associated Quality control Complex

Eukaryotic cells employ the Ribosome-associated Quality control 1 Complex (RQC) to maintain homeostasis despite defects that cause ribosomes to stall. The RQC comprises the E3 ubiquitin ligase Ltn1p, the ATPase Cdc48p, and the novel proteins Rqc1p and Rqc2p. Following recognition and subunit splitti...

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Published inbioRxiv
Main Authors Olga Zurita Rendon, Fredrickson, Eric K, Howard, Conor J, Jonathan Van Vranken, Fogarty, Sarah, Tolley, Neal D, Kalia, Raghav, Osuna, Beatriz A, Shen, Peter S, Hill, Christopher P, Frost, Adam, Rutter, Jared
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 14.04.2018
Subjects
Adenosine triphosphatase
Alanine
Cytosol
Homeostasis
Hydrolase
Lysine
Mitochondria
Organelles
Polypeptides
Proteasomes
Quality control
Ribosomes
Threonine
tRNA
Ubiquitin
Ubiquitin-protein ligase
Ubiquitination
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Summary:Eukaryotic cells employ the Ribosome-associated Quality control 1 Complex (RQC) to maintain homeostasis despite defects that cause ribosomes to stall. The RQC comprises the E3 ubiquitin ligase Ltn1p, the ATPase Cdc48p, and the novel proteins Rqc1p and Rqc2p. Following recognition and subunit splitting of stalled ribosomes, the RQC detects and assembles on 60S subunits that hold incomplete polypeptides linked to a tRNA (60S:peptidyl tRNA). Ltn1p cooperates with Rqc1p to 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, or CAT tails, via a mechanism that is distinct from canonical translation. CAT-tailing mobilizes and exposes lysine residues in the nascent chain, especially those stalled within the exit tunnel, thereby supporting efficient ubiquitination. If the ubiquitin-proteasome system is overwhelmed or unavailable, CAT-tailed nascent chains aggregate in the cytosol or within organelles like the mitochondria. Here we identify Vms1p as the tRNA hydrolase that releases nascent polypeptides for extraction and degradation in the RQC pathway.
DOI:10.1101/301341