Regulation of mRNA levels by decay-promoting introns that recruit the exosome specificity factor Mmi1

Cornelia Kilchert, Sina Wittmann, Monica Passoni, Sneha Shah, Sander Granneman, Lidia Vasiljeva

Research output: Contribution to journalArticlepeer-review

Abstract

In eukaryotic cells, inefficient splicing is surprisingly common and leads to the degradation of transcripts with retained introns. How pre-mRNAs are committed to nuclear decay is unknown. Here, we uncover a mechanism by which specific intron-containing transcripts are targeted for nuclear degradation in fission yeast. Sequence elements within these "decay-promoting" introns co-transcriptionally recruit the exosome specificity factor Mmi1, which induces degradation of the unspliced precursor and leads to a reduction in the levels of the spliced mRNA. This mechanism negatively regulates levels of the RNA helicase DDX5/Dbp2 to promote cell survival in response to stress. In contrast, fast removal of decay-promoting introns by co-transcriptional splicing precludes Mmi1 recruitment and relieves negative expression regulation. We propose that decay-promoting introns facilitate the regulation of gene expression. Based on the identification of multiple additional Mmi1 targets, including mRNAs, long non-coding RNAs, and sn/snoRNAs, we suggest a general role in RNA regulation for Mmi1 through transcript degradation.

Original languageEnglish
Pages (from-to)2504-15
Number of pages12
JournalCell Reports
Volume13
Issue number11
Early online date3 Dec 2015
DOIs
Publication statusPublished - 22 Dec 2015

Keywords

  • splicing
  • mRNA
  • Mmi1
  • RNA exosome
  • RNA decay
  • intron retention

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