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Gene expression

Global analyses of determinants of RNA decay

Nature Reviews Genetics volume 15, page 217 (2014)Cite this article

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Two new studies have carried out analyses of RNA decay rates across the transcriptome in Saccharomyces cerevisiae. Both groups used strains with mutant forms of the RNA polymerase II subunit Rpb1 in order to inducibly block new transcription: Geisberg et al. used an Rbp1 fusion protein that is exported from the nucleus following rapamycin treatment, and Gupta et al. used a temperature-sensitive Rpb1 mutant. The subsequent decay of RNA was monitored using high-throughput sequencing of the 3′ ends of transcripts over time. Both teams found that even subtle alterations to the lengths of 3′ untranslated regions (through alternative polyadenylation of transcript isoforms) could alter mRNA stability. They then characterized the RNA sequence elements for which retention or exclusion during polyadenylation correlated with differential isoform stability. Geisberg et al. showed that a 20-nucleotide poly(U) sequence conferred stability by hybridizing with the poly(A) tail to disfavour binding of RNA-destabilizing proteins (such as poly(A)-binding protein (Pab1)). Gupta et al. showed that binding sites for the Fus3 RNA-binding protein destabilized transcripts. Thus, alternative polyadenylation has widespread roles in regulating mRNA stability through altering sites for RNA-binding proteins.

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References

  1. Geisberg, J. V. et al. Global analysis of mRNA isoform half-lives reveals stabilizing and destabilizing elements in yeast. Cell 156, 812–824 (2014)

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  2. Gupta, I. et al. Alternative polyadenylation diversifies post-transcriptional regulation by selective RNA–protein interactions. Mol. Syst. Biol. 10, 719 (2014)

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  1. Darren J. Burgess
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Burgess, D. Global analyses of determinants of RNA decay. Nat Rev Genet 15, 217 (2014). https://doi.org/10.1038/nrg3710

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