Molecular Biology

Bridging the Genome

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Science  06 Dec 2013:
Vol. 342, Issue 6163, pp. 1147
DOI: 10.1126/science.342.6163.1147-d

Alternative splicing is one means by which the genome is able to generate functional diversity through the differential expression of transcripts, but the regulation and process of how transcripts become alternatively spliced are not well understood. Lovci et al. examined the Rbfox family of RNA-binding proteins with cross-linking immunoprecipitation and sequencing (CLIP-seq) and demonstrated that binding sites are conserved within mammalian genomes and that Rbfox clusters tended to be within distal introns (more than 500 nucleotides away from annotated exons). These clusters were determined to be associated with alternatively spliced exons, with downstream clusters correlating with inclusion of an exon and upstream clusters correlating with the exclusion of the exon. Mutation of Rbfox binding sites in vitro demonstrated that these proteins function in alternative splicing and that conserved RNAs with specific secondary structures bridge the exons that are alternatively spliced. On the basis of these results, the authors propose that a distal binding site of Rbfox proteins is brought into the vicinity of the exon via an RNA bridge.

Nat. Struct. Mol. Biol. 10.1038/nsmb.2699 (2013).

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