The Ccr4-Not complex monitors the translating ribosome for codon optimality

Buschauer, Robert; Matsuo, Yoshitaka; Sugiyama, Takato; Chen, Ying-Hsin; Alhusaini, Najwa; Sweet, Thomas; Ikeuchi, Ken; Cheng, Jingdong; Matsuki, Yasuko; Nobuta, Risa; Gilmozzi, Andrea; Berninghausen, Otto; Tesina, Petr; Becker, Thomas; Coller, Jeff; Inada, Toshifumi und Beckmann, Roland (2020): The Ccr4-Not complex monitors the translating ribosome for codon optimality. In: Science, Bd. 368, Nr. 6488, eaay6912

Abstract

Control of messenger RNA (mRNA) decay rate is intimately connected to translation elongation, but the spatial coordination of these events is poorly understood. The Ccr4-Not complex initiates mRNA decay through deadenylation and activation of decapping. We used a combination of cryo-electron microscopy, ribosome profiling, and mRNA stability assays to examine the recruitment of Ccr4-Not to the ribosome via specific interaction of the Not5 subunit with the ribosomal E-site in Saccharomyces cerevisiae. This interaction occurred when the ribosome lacked accommodated A-site transfer RNA, indicative of low codon optimality. Loss of the interaction resulted in the inability of the mRNA degradation machinery to sense codon optimality. Our findings elucidate a physical link between the Ccr4-Not complex and the ribosome and provide mechanistic insight into the coupling of decoding efficiency with mRNA stability.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department Biochemie
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 0036-8075
• Sprache: Englisch