The Ccr4-Not complex monitors the translating ribosome for codon optimality
Robert Buschauer, Yoshitaka Matsuo, Takato Sugiyama, Ying-Hsin Chen, Najwa Alhusaini, Thomas J. Sweet, Ken Ikeuchi, Jingdong Cheng, Yasuko Matsuki, Risa Nobuta, Andrea Gilmozzi, Otto Berninghausen, Petr Těšina, Thomas Becker, Jeff Coller, Toshifumi Inada, Roland Beckmann
Abstract
Coupling translation and mRNA decay Gene expression requires messenger RNAs (mRNAs)—DNA-derived blueprints of genes—to be translated by protein-producing ribosomes. The levels of mRNAs are tightly regulated, in part by controlling their half-lives. In eukaryotic cells, mRNA half-life is largely linked to translational efficiency, but the mechanism underlying this link has remained elusive. Buschauer et al. used cryo–electron microscopy and RNA sequencing to show how a key regulator of mRNA degradation, the Ccr4-Not complex, monitors the ribosome during mRNA translation. They found that the Not5 subunit directly binds to a ribosomal site exposed specifically during inefficient decoding, thereby triggering mRNA degradation. Analysis of mutants revealed the importance of this sensing mechanism for mRNA homeostasis. Science , this issue p. eaay6912