RQT complex dissociates ribosomes collided on endogenous RQC substrate SDD1

Nat Struct Mol Biol. 2020 Apr;27(4):323-332. doi: 10.1038/s41594-020-0393-9. Epub 2020 Mar 23.


Ribosome-associated quality control (RQC) represents a rescue pathway in eukaryotic cells that is triggered upon translational stalling. Collided ribosomes are recognized for subsequent dissociation followed by degradation of nascent peptides. However, endogenous RQC-inducing sequences and the mechanism underlying the ubiquitin-dependent ribosome dissociation remain poorly understood. Here, we identified SDD1 messenger RNA from Saccharomyces cerevisiae as an endogenous RQC substrate and reveal the mechanism of its mRNA-dependent and nascent peptide-dependent translational stalling. In vitro translation of SDD1 mRNA enabled the reconstitution of Hel2-dependent polyubiquitination of collided disomes and, preferentially, trisomes. The distinct trisome architecture, visualized using cryo-EM, provides the structural basis for the more-efficient recognition by Hel2 compared with that of disomes. Subsequently, the Slh1 helicase subunit of the RQC trigger (RQT) complex preferentially dissociates the first stalled polyubiquitinated ribosome in an ATP-dependent manner. Together, these findings provide fundamental mechanistic insights into RQC and its physiological role in maintaining cellular protein homeostasis.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / chemistry
  • Adenosine Triphosphate / genetics
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / ultrastructure*
  • Peptides / chemistry
  • Peptides / genetics
  • Protein Biosynthesis*
  • RNA, Messenger / genetics
  • Ribosomes / chemistry
  • Ribosomes / genetics*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / ultrastructure*
  • Serine Endopeptidases / chemistry
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / ultrastructure*
  • Ubiquitin / chemistry
  • Ubiquitin / genetics
  • Ubiquitin-Protein Ligases / chemistry
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / ultrastructure*
  • Ubiquitination / genetics


  • Cell Cycle Proteins
  • Peptides
  • RNA, Messenger
  • SDD1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Ubiquitin
  • Adenosine Triphosphate
  • Hel2 protein, S cerevisiae
  • Ubiquitin-Protein Ligases
  • Serine Endopeptidases