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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 publication

DOI

10.1016/j.celrep.2015.11.026

Type

Journal article

Journal

Cell Rep

Publication Date

22/12/2015

Volume

13

Pages

2504 - 2515

Keywords

Mmi1, RNA decay, RNA exosome, intron retention, mRNA, splicing, Base Sequence, Chromatin Immunoprecipitation, DEAD-box RNA Helicases, Exosomes, Gene Expression Regulation, Fungal, Introns, Protein Binding, RNA Precursors, RNA Splicing, RNA Stability, RNA, Messenger, RNA, Untranslated, Schizosaccharomyces, Schizosaccharomyces pombe Proteins, Sequence Analysis, RNA, Transcriptome, mRNA Cleavage and Polyadenylation Factors