Decoding of the ubiquitin code for clearance of colliding ribosomes by the RQT complex

• Published in: Nature communications Vol. 14; no. 1; p. 79
• Main Authors: Matsuo, Yoshitaka, Uchihashi, Takayuki, Inada, Toshifumi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.01.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 38; 631/45/500; 631/45/612/1254; 82/83; Antibodies; Atomic force microscopy; Chains; Clearances; Decoding; Domains; Experiments; Humanities and Social Sciences; Microscopy; multidisciplinary; Mutation; Protein Biosynthesis; Proteins; Quality control; Ribosomes; Ribosomes - metabolism; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Science; Science (multidisciplinary); Ubiquitin; Ubiquitin - metabolism; Ubiquitin-Protein Ligases - metabolism; Ubiquitination; Yeast
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-35608-4

The collision sensor Hel2 specifically recognizes colliding ribosomes and ubiquitinates the ribosomal protein uS10, leading to noncanonical subunit dissociation by the ribosome-associated quality control trigger (RQT) complex. Although uS10 ubiquitination is essential for rescuing stalled ribosomes, its function and recognition steps are not fully understood. Here, we show that the RQT complex components Cue3 and Rqt4 interact with the K63-linked ubiquitin chain and accelerate the recruitment of the RQT complex to the ubiquitinated colliding ribosome. The CUE domain of Cue3 and the N-terminal domain of Rqt4 bind independently to the K63-linked ubiquitin chain. Their deletion abolishes ribosomal dissociation mediated by the RQT complex. High-speed atomic force microscopy (HS-AFM) reveals that the intrinsically disordered regions of Rqt4 enable the expansion of the searchable area for interaction with the ubiquitin chain. These findings provide mechanistic insight into the decoding of the ubiquitin code for clearance of colliding ribosomes by the RQT complex. The colliding ribosomes are ubiquitinated by the sensor protein Hel2, leading to noncanonical subunit dissociation by the ribosome associated quality control trigger (RQT) complex. Here the authors reveal the decoding mechanism of the ribosome ubiquitin code by the RQT complex.