Decoding of the ubiquitin code for clearance of colliding ribosomes by the RQT complex

Nat Commun. 2023 Jan 10;14(1):79. doi: 10.1038/s41467-022-35608-4.


The collision sensor Hel2 specifically recognizes colliding ribosomes and ubiquitinates the ribosomal protein uS10, leading to noncanonical subunit dissociation by the ribosome-associated quality control trigger (RQT) complex. Although uS10 ubiquitination is essential for rescuing stalled ribosomes, its function and recognition steps are not fully understood. Here, we show that the RQT complex components Cue3 and Rqt4 interact with the K63-linked ubiquitin chain and accelerate the recruitment of the RQT complex to the ubiquitinated colliding ribosome. The CUE domain of Cue3 and the N-terminal domain of Rqt4 bind independently to the K63-linked ubiquitin chain. Their deletion abolishes ribosomal dissociation mediated by the RQT complex. High-speed atomic force microscopy (HS-AFM) reveals that the intrinsically disordered regions of Rqt4 enable the expansion of the searchable area for interaction with the ubiquitin chain. These findings provide mechanistic insight into the decoding of the ubiquitin code for clearance of colliding ribosomes by the RQT complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Protein Biosynthesis
  • Ribosomes / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomyces cerevisiae Proteins* / metabolism
  • Ubiquitin* / metabolism
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination


  • Ubiquitin
  • Saccharomyces cerevisiae Proteins
  • Hel2 protein, S cerevisiae
  • Ubiquitin-Protein Ligases