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; Inada, Toshifumi
(2017):
Ubiquitination of stalled ribosome triggers ribosome-associated quality control.
In: Nature Communications, Vol. 8, 159
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![[img]](https://epub.ub.uni-muenchen.de/54121/1.hassmallThumbnailVersion/s41467-017-00188-1.pdf)  Preview |
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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.