Citation:
Nat Struct Mol Biol. 2013 Nov 10. doi: 10.1038/nsmb.2699. [Epub ahead of print]
Abstract:
Alternative splicing (AS) enables programmed diversity of gene expression across tissues and development. We show here that binding in distal intronic regions (>500 nucleotides (nt) from any exon) by Rbfox splicing factors important in development is extensive and is an active mode of splicing regulation. Similarly to exon-proximal sites, distal sites contain evolutionarily conserved GCATG sequences and are associated with AS activation and repression upon modulation of Rbfox abundance in human and mouse experimental systems. As a proof of principle, we validated the activity of two specific Rbfox enhancers in KIF21A and ENAH distal introns and showed that a conserved long-range RNA-RNA base-pairing interaction (an RNA bridge) is necessary for Rbfox-mediated exon inclusion in the ENAH gene. Thus we demonstrate a previously unknown RNA-mediated mechanism for AS control by distally bound RNA-binding proteins.
Epub:
Yes
Link to Publication:
http://www.nature.com/nsmb/journal/vaop/ncurrent/full/nsmb.2699.html
Organism or Cell Type:
mouse, cell culture: HS578T cells
Delivery Method:
Vivo-Morpholino in vivo, Endo-Porter in culture