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Decapping is preceded by 3′ uridylation in a novel pathway of bulk mRNA turnover

Nature Structural & Molecular Biology volume 16, pages 616–623 (2009)Cite this article

Abstract

Both end structures of eukaryotic mRNAs, namely the 5′ cap and 3′ poly(A) tail, are necessary for transcript stability, and loss of either is sufficient to stimulate decay. mRNA turnover is classically thought to be initiated by deadenylation, as has been particularly well described in Saccharomyces cerevisiae. Here we describe two additional, parallel decay pathways in the fission yeast Schizosaccharomyces pombe. First, in fission yeast mRNA decapping is frequently independent of deadenylation. Second, Cid1-dependent uridylation of polyadenylated mRNAs, such as act1, hcn1 and urg1, seems to stimulate decapping as part of a novel mRNA turnover pathway. Accordingly, urg1 mRNA is stabilized in cid1Δ cells. Uridylation and deadenylation act redundantly to stimulate decapping, and our data suggest that uridylation-dependent decapping is mediated by the Lsm1–7 complex. As human cells contain Cid1 orthologs, uridylation may form the basis of a widespread, conserved mechanism of mRNA decay.

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Figure 1: Decapping of mRNA can be independent of deadenylation.
Figure 2: Decapped mRNAs are often uridylated.
Figure 3: mRNA uridylation is Cid1-dependent, and impairment of decapping increases uridylation on decapped messages.
Figure 4: Uridylation precedes decapping.
Figure 5: urg1 mRNA is more stable in cells lacking Cid1.
Figure 6: Deadenylation and uridylation function as redundant pathways in mRNA decay.
Figure 7: Uridylation-mediated decapping requires Lsm1.
Figure 8: A comparison of decay pathways for bulk mRNA in S. cerevisiae and S. pombe.

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Acknowledgements

We thank D. Bartel for his support. We also thank other members of the laboratory, A. Woollard, E. Wahle and N. Proudfoot for helpful discussions and critical reading of the manuscript, as well as T. Katada (University of Tokyo) for providing various strains. This work was supported by Cancer Research UK and the Biotechnologies and Biological Sciences Research Council. O.S.R. was supported by a scholarship from the Rhodes Trust.

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  1. Olivia S Rissland

    Present address: Present address: Whitehead Institute, Cambridge, Massachusetts, USA.,

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  1. Sir William Dunn School of Pathology, University of Oxford, UK

    Olivia S Rissland & Chris J Norbury

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O.S.R. performed all the experimental work; O.S.R. and C.J.N. designed the experiments, interpreted the data and wrote the manuscript.

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Correspondence to Chris J Norbury.

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Rissland, O., Norbury, C. Decapping is preceded by 3′ uridylation in a novel pathway of bulk mRNA turnover. Nat Struct Mol Biol 16, 616–623 (2009). https://doi.org/10.1038/nsmb.1601

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