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

Journal article

In eukaryotic cells, inefficient splicing is surprisingly common and leads to 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 of 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 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.

Authors: Kilchert, C; Wittmann, S; Passoni, M; Shah, S; Granneman, S

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Cell Press
• Journal: Cell Reports
• Volume: 13
• Issue: 11
• Pages: 2504-2515
• Publication date: 2015-01-01
• DOI: 10.1016/j.celrep.2015.11.026
• ISSN: 2211-1247
• Language: English
• Keywords: regulation of gene expression; splicing; RNA exosome; Mmi1; mRNA; RNA decay; intron retention