Identification of a novel trigger complex that facilitates ribosome-associated quality control in mammalian cells

Sci Rep. 2020 Feb 25;10(1):3422. doi: 10.1038/s41598-020-60241-w.


Ribosome stalling triggers the ribosome-associated quality control (RQC) pathway, which targets collided ribosomes and leads to subunit dissociation, followed by proteasomal degradation of the nascent peptide. In yeast, RQC is triggered by Hel2-dependent ubiquitination of uS10, followed by subunit dissociation mediated by the RQC-trigger (RQT) complex. In mammals, ZNF598-dependent ubiquitination of collided ribosomes is required for RQC, and activating signal cointegrator 3 (ASCC3), a component of the ASCC complex, facilitates RQC. However, the roles of other components and associated factors of the ASCC complex remain unknown. Here, we demonstrate that the human RQC-trigger (hRQT) complex, an ortholog of the yeast RQT complex, plays crucial roles in RQC. The hRQT complex is composed of ASCC3, ASCC2, and TRIP4, which are orthologs of the RNA helicase Slh1(Rqt2), ubiquitin-binding protein Cue3(Rqt3), and zinc-finger type protein yKR023W(Rqt4), respectively. The ATPase activity of ASCC3 and the ubiquitin-binding activity of ASCC2 are crucial for triggering RQC. Given the proposed function of the RQT complex in yeast, we propose that the hRQT complex recognizes the ubiquitinated stalled ribosome and induces subunit dissociation to facilitate RQC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Helicases / genetics
  • DNA Helicases / metabolism
  • HEK293 Cells
  • Humans
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Ribosomes / genetics
  • Ribosomes / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • ASCC2 protein, human
  • Multiprotein Complexes
  • Nuclear Proteins
  • Saccharomyces cerevisiae Proteins
  • TRIP4 protein, human
  • Transcription Factors
  • ASCC3 protein, human
  • DNA Helicases