Drosha promotes splicing of a pre-microRNA-like alternative exon.

Abstract:

:The ribonuclease III enzyme Drosha has a central role in the biogenesis of microRNA (miRNA) by binding and cleaving hairpin structures in primary RNA transcripts into precursor miRNAs (pre-miRNAs). Many miRNA genes are located within protein-coding host genes and cleaved by Drosha in a manner that is coincident with splicing of introns by the spliceosome. The close proximity of splicing and pre-miRNA biogenesis suggests a potential for co-regulation of miRNA and host gene expression, though this relationship is not completely understood. Here, we describe a cleavage-independent role for Drosha in the splicing of an exon that has a predicted hairpin structure resembling a Drosha substrate. We find that Drosha can cleave the alternatively spliced exon 5 of the eIF4H gene into a pre-miRNA both in vitro and in cells. However, the primary role of Drosha in eIF4H gene expression is to promote the splicing of exon 5. Drosha binds to the exon and enhances splicing in a manner that depends on RNA structure but not on cleavage by Drosha. We conclude that Drosha can function like a splicing enhancer and promote exon inclusion. Our results reveal a new mechanism of alternative splicing regulation involving a cleavage-independent role for Drosha in splicing.

journal_name

PLoS Genet

journal_title

PLoS genetics

authors

Havens MA,Reich AA,Hastings ML

doi

10.1371/journal.pgen.1004312

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

e1004312

issue

5

eissn

1553-7390

issn

1553-7404

pii

PGENETICS-D-13-03029

journal_volume

10

pub_type

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