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Publication : A competitive regulatory mechanism discriminates between juxtaposed splice sites and pri-miRNA structures.

First Author  Mattioli C Year  2013
Journal  Nucleic Acids Res Volume  41
Issue  18 Pages  8680-91
PubMed ID  23863840 Mgi Jnum  J:210405
Mgi Id  MGI:5571009 Doi  10.1093/nar/gkt614
Citation  Mattioli C, et al. (2013) A competitive regulatory mechanism discriminates between juxtaposed splice sites and pri-miRNA structures. Nucleic Acids Res 41(18):8680-91
abstractText  We have explored the functional relationships between spliceosome and Microprocessor complex activities in a novel class of microRNAs (miRNAs), named Splice site Overlapping (SO) miRNAs, whose pri-miRNA hairpins overlap splice sites. We focused on the evolutionarily conserved SO miR-34b, and we identified two indispensable elements for recognition of its 3' splice site: a branch point located in the hairpin and a downstream purine-rich exonic splicing enhancer. In minigene systems, splicing inhibition owing to exonic splicing enhancer deletion or AG 3'ss mutation increases miR-34b levels. Moreover, small interfering-mediated silencing of Drosha and/or DGCR8 improves splicing efficiency and abolishes miR-34b production. Thus, the processing of this 3' SO miRNA is regulated in an antagonistic manner by the Microprocessor and the spliceosome owing to competition between these two machineries for the nascent transcript. We propose that this novel mechanism is commonly used to regulate the relative amount of SO miRNA and messenger RNA produced from primary transcripts.
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