Canonical Poly(A) Polymerase Activity Promotes the Decay of a Wide Variety of Mammalian Nuclear RNAs

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Cells control gene expression by balancing the rates of RNA synthesis and decay. While the mechanisms of transcription regulation are extensively studied, the parameters that control nuclear RNA stability remain largely unknown. Previously, we and others reported that poly(A) tails may stimulate RNA decay in mammalian nuclei. This function is mediated by the concerted actions of the nuclear poly(A) binding protein PABPN1, poly(A) polymerase (PAP), and the nuclear exosome complex, a pathway we have named PABPN1 and PAP-mediated RNA decay (PPD). Because nearly all mRNAs possess a poly(A) tail, it remains unclear how PPD targets specific transcripts. Here, we inactivated PPD by two distinct mechanisms and examined global gene expression. We identified a number of potential target genes, including snoRNA host genes, promoter antisense RNAs, and mRNAs. Interestingly, target transcripts tend to be incompletely spliced or possess fewer introns than non-target transcripts, suggesting that efficient splicing allows normal mRNAs to escape decay. We suggest that PPD plays an important role in gene expression by limiting the accumulation of inefficiently processed RNAs. In addition, our results highlight the complex relationship between (pre-)mRNA splicing and nuclear RNA decay.

Vyšlo v časopise: Canonical Poly(A) Polymerase Activity Promotes the Decay of a Wide Variety of Mammalian Nuclear RNAs. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005610
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005610

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