Collided ribosomes form a unique structural interface to induce Hel2-driven quality control pathways

Ken Ikeuchi, Petr Tesina, Yoshitaka Matsuo, Takato Sugiyama, Jingdong Cheng, Yasushi Saeki, Keiji Tanaka, Thomas Becker, Roland Beckmann, Toshifumi Inada

Research output: Contribution to journalArticlepeer-review

92 Citations (Scopus)

Abstract

Ribosome stalling triggers quality control pathways targeting the mRNA (NGD: no-go decay) and the nascent polypeptide (RQC: ribosome-associated quality control). RQC requires Hel2-dependent uS10 ubiquitination and the RQT complex in yeast. Here, we report that Hel2-dependent uS10 ubiquitination and Slh1/Rqt2 are crucial for RQC and NGD induction within a di-ribosome (disome) unit, which consists of the leading stalled ribosome and the following colliding ribosome. Hel2 preferentially ubiquitinated a disome over a monosome on a quality control inducing reporter mRNA in an in vitro translation reaction. Cryo-EM analysis of the disome unit revealed a distinct structural arrangement suitable for recognition and modification by Hel2. The absence of the RQT complex or uS10 ubiquitination resulted in the elimination of NGD within the disome unit. Instead, we observed Hel2-mediated cleavages upstream of the disome, governed by initial Not4-mediated monoubiquitination of eS7 and followed by Hel2-mediated K63-linked polyubiquitination. We propose that Hel2-mediated ribosome ubiquitination is required both for canonical NGD (NGD RQC + ) and RQC coupled to the disome and that RQC-uncoupled NGD outside the disome (NGD RQC ) can occur in a Not4-dependent manner.

Original languageEnglish
Article numbere100276
JournalEMBO Journal
Volume38
Issue number5
DOIs
Publication statusPublished - 2019 Mar 1

Keywords

  • RQT complex
  • no-go mRNA decay
  • ribosome collision
  • ribosome quality control
  • ubiquitination

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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