2010 Rustbelt RNA Meeting
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Talk on Friday 02:15-02:30pm submitted by Mallory Havens

Biogenesis of Mirtrons Independent of Splicing and the Microprocessor

Mallory A. Havens (Cell Biology and Anatomy, Chicago Medical School at Rosalind Franklin University, North Chicago, IL, USA), Ashley A. Reich (Department of Biology, Lake Forest College, Lake Forest, IL, USA), Michelle L. Hastings (Cell Biology and Anatomy, Chicago Medical School at Rosalind Franklin University, North Chicago, IL, USA)

Abstract:
Mirtrons are a recently discovered class of microRNA that are generated by a nuclear processing pathway that is distinct from canonical miRNAs. Mirtrons are defined by their dependence on splicing and debranching of the excised intron lariat, rather than the miRNA microprocessor complex, for the production of the pre-miRNA. Mirtrons were first described in Drosophila and have been predicted, but are yet to be experimentally validated, in humans. To examine the processing of putative mirtrons in humans, we constructed a number of minigenes comprised of a mirtron-containing intron and the flanking exons. We found that production of some of the predicted mirtrons depended on splicing of the intron, however, a number of them were still produced when splicing was abolished by mutation of the splice sites. Surprisingly, the abundance of these same splicing-independent mirtrons was not reduced by knockdown of the microprocessor component, DGCR8. Our results suggest that there may be a subclass of microRNAs that can be processed from a primary RNA transcript by a currently unknown mechanism that does not involve the traditional mirtron or microprocessor pathways.

Keywords: Mirtron, microRNA biogenesis, Splicing