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

Area of Science:

• Molecular Biology
• Biochemistry
• Genetics

Background:

• Messenger RNA (mRNA) decay rate is crucial for gene expression regulation.
• The Ccr4-Not complex is a key regulator of mRNA decay, initiating deadenylation and decapping.
• The spatial coordination between translation elongation and mRNA decay is not well understood.

Purpose of the Study:

• To investigate the physical interaction between the Ccr4-Not complex and the ribosome.
• To understand how this interaction influences mRNA decay in response to translation efficiency.
• To elucidate the mechanism coupling decoding efficiency with mRNA stability.

Main Methods:

• Cryo-electron microscopy (cryo-EM) to visualize complex structures.
• Ribosome profiling to assess translation dynamics.
• mRNA stability assays to measure decay rates in *Saccharomyces cerevisiae*.

Main Results:

• Identified a specific interaction between the Not5 subunit of Ccr4-Not and the ribosomal E-site.
• This interaction occurs when the ribosome lacks an accommodated A-site transfer RNA, indicating low codon optimality.
• Disruption of this interaction impairs the mRNA degradation machinery's ability to sense codon optimality.

Conclusions:

• Established a direct physical link between the Ccr4-Not complex and the ribosome.
• Provided mechanistic insight into how decoding efficiency (codon optimality) is coupled to mRNA stability.
• Revealed a novel regulatory mechanism controlling mRNA decay based on translation conditions.