RRC ID 64245
Author Kilchert C, Wittmann S, Passoni M, Shah S, Granneman S, Vasiljeva L.
Title Regulation of mRNA Levels by Decay-Promoting Introns that Recruit the Exosome Specificity Factor Mmi1.
Journal Cell Rep
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.
Volume 13(11)
Pages 2504-2515
Published 2015-12-22
DOI 10.1016/j.celrep.2015.11.026
PII S2211-1247(15)01326-1
PMID 26670050
PMC PMC4695336
MeSH Base Sequence Chromatin Immunoprecipitation DEAD-box RNA Helicases / metabolism Exosomes / metabolism* Gene Expression Regulation, Fungal Introns Protein Binding RNA Precursors / metabolism RNA Splicing RNA Stability RNA, Messenger / metabolism* RNA, Untranslated / metabolism Schizosaccharomyces / genetics Schizosaccharomyces / metabolism* Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism* Sequence Analysis, RNA Transcriptome mRNA Cleavage and Polyadenylation Factors / genetics mRNA Cleavage and Polyadenylation Factors / metabolism*
Resource
Yeast FY23475, FY9118