CAT-tailing as a Fail-Safe Mechanism for Efficient Degradation of Stalled Nascent Polypeptides

Science. 2017 Jul 28;357(6349):414-417. doi: 10.1126/science.aam7787.

Abstract

Ribosome stalling leads to recruitment of the ribosome quality control complex (RQC), which targets the partially synthesized polypeptide for proteasomal degradation through the action of the ubiquitin ligase Ltn1p. A second core RQC component, Rqc2p, modifies the nascent polypeptide by adding a carboxyl-terminal alanine and threonine (CAT) tail through a noncanonical elongation reaction. Here we examined the role of CAT-tailing in nascent-chain degradation in budding yeast. We found that Ltn1p efficiently accessed only nascent-chain lysines immediately proximal to the ribosome exit tunnel. For substrates without Ltn1p-accessible lysines, CAT-tailing enabled degradation by exposing lysines sequestered in the ribosome exit tunnel. Thus, CAT-tails do not serve as a degron, but rather provide a fail-safe mechanism that expands the range of RQC-degradable substrates.

Publication types

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

MeSH terms

  • Alanine / chemistry
  • Alanine / metabolism
  • Lysine / chemistry
  • Lysine / metabolism
  • Peptides / chemistry
  • Peptides / metabolism*
  • Proteolysis*
  • Proteostasis*
  • Ribosomes / metabolism*
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Threonine / chemistry
  • Threonine / metabolism
  • Transcription Elongation, Genetic*
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases / chemistry
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • Peptides
  • Saccharomyces cerevisiae Proteins
  • Ubiquitin
  • Threonine
  • Ltn1 protein, S cerevisiae
  • Ubiquitin-Protein Ligases
  • Lysine
  • Alanine