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bioRxiv · 10.1101/854810

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

Buschauer, R.·Matsuo, Y.·Chen, Y.-H.·Alhusaini, N.·Sweet, T.·Sugiyama, T.·Ikeuchi, K.·Cheng, J.·Matsuki, Y.·Gilmozzi, A.·Berninghausen, O.·Becker, T.·Coller, J.·Inada, T.·Beckmann, R.
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Abstract

Control of 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. Using a combination of cryo-electron microscopy, ribosome profiling and mRNA stability assays we show recruitment of Ccr4-Not to the ribosome via specific interaction of the Not5 subunit with the ribosomal E-site. This interaction only occurs when the ribosome lacks accommodated A-site tRNA, indicative of low codon optimality. Loss of Not5 results in the inability of the mRNA degradation machinery to sense codon optimality. Our analysis elucidates a physical link between the Ccr4-Not complex and the ribosome providing mechanistic insight into the coupling of decoding efficiency with mRNA stability.

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Buschauer, R., Matsuo, Y., Chen, Y.-H., Alhusaini, N., Sweet, T., Sugiyama, T., Ikeuchi, K., Cheng, J., Matsuki, Y., Gilmozzi, A., Berninghausen, O., Becker, T., Coller, J., Inada, T., Beckmann, R.. 2019-11-25. The Ccr4-Not complex monitors the translating ribosome for codon optimality. https://doi.org/10.1101/854810

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