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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Peptides / genetics
  • Peptides / metabolism
  • Protein Binding
  • Protein Biosynthesis / genetics*
  • Quality Control
  • RNA, Transfer, Amino Acyl / genetics
  • RNA, Transfer, Amino Acyl / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Ribosome Subunits, Large, Eukaryotic / genetics*
  • Ribosome Subunits, Large, Eukaryotic / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • Valosin Containing Protein / genetics
  • Valosin Containing Protein / metabolism


  • Carrier Proteins
  • Multiprotein Complexes
  • Peptides
  • RNA, Transfer, Amino Acyl
  • RNA-Binding Proteins
  • Rqc1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Tae2 protein, S cerevisiae
  • Vms1 protein, S cerevisiae
  • tRNA, peptidyl-
  • Ltn1 protein, S cerevisiae
  • Ubiquitin-Protein Ligases
  • CDC48 protein, S cerevisiae
  • Valosin Containing Protein