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

Robert Buschauer, Yoshitaka Matsuo, Takato Sugiyama, Ying Hsin Chen, Najwa Alhusaini, Thomas Sweet, Ken Ikeuchi, Jingdong Cheng, Yasuko Matsuki, Risa Nobuta, Andrea Gilmozzi, Otto Berninghausen, Petr Tesina, Thomas Becker, Jeff Coller, Toshifumi Inada, Roland Beckmann

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

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.

Original languageEnglish
Article numbereaay6912
JournalScience
Volume368
Issue number6488
DOIs
Publication statusPublished - 2020 Apr 17
Externally publishedYes

ASJC Scopus subject areas

  • General

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