Systematic discovery of regulated and conserved alternative exons in the mammalian brain reveals NMD modulating chromatin regulators
Abstract
Alternative splicing (AS) plays an important role in the mammalian brain, but our atlas of AS events is incomplete. Here, we conducted comprehensive analysis of deep RNA-Seq data of mouse cortex to identify new AS events and evaluate their functionality. We expanded the number of annotated AS events more than 10-fold and demonstrated that, like many known events, thousands of newly discovered events are regulated, conserved, and likely functional. In particular, some can regulate gene expression levels through nonsense-mediated decay, a known mechanism for RNA binding protein autoregulation. Surprisingly, we discovered a number of chromatin regulators as novel targets of this mechanism, revealing a new regulatory link between epigenetics and AS that primarily emerged in the mammalian lineage.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- March 2015
- DOI:
- Bibcode:
- 2015PNAS..112.3445Y