Co-translational mRNA decay in Saccharomyces cerevisiae

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Abstract

The rates of RNA decay and transcription determine the steady-state levels of all messenger RNA and both can be subject to regulation. Although the details of transcriptional regulation are becoming increasingly understood, the mechanism(s) controlling mRNA decay remain unclear. In yeast, a major pathway of mRNA decay begins with deadenylation followed by decapping and 5′–3′ exonuclease digestion. Importantly, it is hypothesized that ribosomes must be removed from mRNA before transcripts are destroyed. Contrary to this prediction, here we show that decay takes place while mRNAs are associated with actively translating ribosomes. The data indicate that dissociation of ribosomes from mRNA is not a prerequisite for decay and we suggest that the 5′–3′ polarity of mRNA degradation has evolved to ensure that the last translocating ribosome can complete translation.

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Figure 1: Decapped mRNA is associated with polyribosomes.
Figure 2: mRNA decapping is initiated on polyribosomes.
Figure 3: mRNA decapping occurs on polyribosomes in wild-type cells.

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Acknowledgements

We thank P. Maroney and T. Nilsen for sharing unpublished data about the poly(A) tailing assay. We also thank T. Nilsen for his insight, suggestions and evaluation of the manuscript. We also thank R. Parker, A. van Hoof and M. Wickens for reagents and advice. Funding was provided by the American Heart Association and the National Institutes of Health.

Author Contributions W.H., K.E.B. and J.C. wrote the manuscript. W.H. and T.J.S. performed the experiments. S.C. provided technical expertise with poly(A) tailing assays. All of the authors contributed to discussion and the design of the research. All authors commented on the manuscript.

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Correspondence to Jeff Coller.

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Hu, W., Sweet, T., Chamnongpol, S. et al. Co-translational mRNA decay in Saccharomyces cerevisiae. Nature 461, 225–229 (2009) doi:10.1038/nature08265

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