Sensing of individual stalled 80S ribosomes by Fap1 for nonfunctional rRNA turnover

Li, Sihan; Ikeuchi, Ken; Kato, Misaki; Buschauer, Robert; Sugiyama, Takato; Adachi, Shungo; Kusano, Hideo; Natsume, Tohru; Berninghausen, Otto; Matsuo, Yoshitaka; Becker, Thomas; Beckmann, Roland und Inada, Toshifumi (2022): Sensing of individual stalled 80S ribosomes by Fap1 for nonfunctional rRNA turnover. In: Molecular Cell, Bd. 82, Nr. 18, E8: S. 3424-3437

Abstract

Cells can respond to stalled ribosomes by sensing ribosome collisions and employing quality control path-ways. How ribosome stalling is resolved without collisions, however, has remained elusive. Here, focusing on noncolliding stalling exhibited by decoding-defective ribosomes, we identified Fap1 as a stalling sensor trig-gering 18S nonfunctional rRNA decay via polyubiquitination of uS3. Ribosome profiling revealed an enrich-ment of Fap1 at the translation initiation site but also an association with elongating individual ribosomes. Cryo-EM structures of Fap1-bound ribosomes elucidated Fap1 probing the mRNA simultaneously at both the entry and exit channels suggesting an mRNA stasis sensing activity, and Fap1 sterically hinders the formation of canonical collided di-ribosomes. Our findings indicate that individual stalled ribosomes are the potential signal for ribosome dysfunction, leading to accelerated turnover of the ribosome itself.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department für Pharmazie - Zentrum für Pharmaforschung ; Chemie und Pharmazie > Department Biochemie
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 1097-2765
• Sprache: Englisch