Regulation of mRNA Levels by Suicidal Introns that Induce Nuclear Decay



Expression profiling by high throughput sequencing.
Non-coding RNA profiling by high throughput sequencing


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 intronic transcripts are targeted for nuclear degradation in fission yeast. Surprisingly, sequence elements within “suicidal” introns co-transcriptionally recruit the exosome adaptor Mmi1 not only to degrade unspliced precursor, but also to downregulate levels of the resulting mRNA. Under conditions permissive for fast splicing, Mmi1 is no longer recruited and negative expression regulation is relieved. This mechanism negatively regulates levels of the RNA-helicase DDX5/Dbp2 to ensure cell survival in response to stress. We propose that suicidal introns are maintained because they facilitate regulation of gene expression. We identify multiple novel Mmi1 targets including mRNAs, non-coding RNAs, and sn/snoRNAs. We suggest a general role in RNA regulation for Mmi1 beyond degradation of meiotic transcripts.

Data Citation

Kilchert C, Wittmann S, Passoni M, Shah S et al. Regulation of mRNA Levels by Decay-Promoting Introns that Recruit the Exosome Specificity Factor Mmi1. Cell Rep 2015 Dec 22;13(11):2504-2515. PMID: 26670050

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