Ubiquitination of stalled ribosome triggers ribosome-associated quality control

Yoshitaka Matsuo, Ken Ikeuchi, Yasushi Saeki, Shintaro Iwasaki, Christian Schmidt, Tsuyoshi Udagawa, Fumiya Sato, Hikaru Tsuchiya, Thomas Becker, Keiji Tanaka, Nicholas T. Ingolia, Roland Beckmann, Toshifumi Inada

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Translation arrest by polybasic sequences induces ribosome stalling, and the arrest product is degraded by the ribosome-mediated quality control (RQC) system. Here we report that ubiquitination of the 40S ribosomal protein uS10 by the E3 ubiquitin ligase Hel2 (or RQT1) is required for RQC. We identify a RQC-trigger (RQT) subcomplex composed of the RNA helicase-family protein Slh1/Rqt2, the ubiquitin-binding protein Cue3/Rqt3, and yKR023W/Rqt4 that is required for RQC. The defects in RQC of the RQT mutants correlate with sensitivity to anisomycin, which stalls ribosome at the rotated form. Cryo-electron microscopy analysis reveals that Hel2-bound ribosome are dominantly the rotated form with hybrid tRNAs. Ribosome profiling reveals that ribosomes stalled at the rotated state with specific pairs of codons at P-A sites serve as RQC substrates. Rqt1 specifically ubiquitinates these arrested ribosomes to target them to the RQT complex, allowing subsequent RQC reactions including dissociation of the stalled ribosome into subunits.

Original languageEnglish
Article number159
JournalNature communications
Volume8
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'Ubiquitination of stalled ribosome triggers ribosome-associated quality control'. Together they form a unique fingerprint.

  • Cite this

    Matsuo, Y., Ikeuchi, K., Saeki, Y., Iwasaki, S., Schmidt, C., Udagawa, T., Sato, F., Tsuchiya, H., Becker, T., Tanaka, K., Ingolia, N. T., Beckmann, R., & Inada, T. (2017). Ubiquitination of stalled ribosome triggers ribosome-associated quality control. Nature communications, 8(1), [159]. https://doi.org/10.1038/s41467-017-00188-1