Ubiquitination of stalled ribosome triggers ribosome-associated quality control

Matsuo, Yoshitaka; Ikeuchi, Ken; Saeki, Yasushi; Iwasaki, Shintaro; Schmidt, Christian; Udagawa, Tsuyoshi; Sato, Fumiya; Tsuchiya, Hikaru; Becker, Thomas; Tanaka, Keiji; Ingolia, Nicholas T.; Beckmann, Roland and Inada, Toshifumi (2017): Ubiquitination of stalled ribosome triggers ribosome-associated quality control. In: Nature Communications, Vol. 8, 159

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.

• Item Type: Journal article
• Faculties: Chemistry and Pharmacy > Department of Biochemistry
• Subjects: 500 Science > 540 Chemistry
• ISSN: 2041-1723
• Language: English