Overlapping splicing regulatory motifs--combinatorial effects on splicing.

Nucleic Acids Research
Amir GorenGil Ast

Abstract

Regulation of splicing in eukaryotes occurs through the coordinated action of multiple splicing factors. Exons and introns contain numerous putative binding sites for splicing regulatory proteins. Regulation of splicing is presumably achieved by the combinatorial output of the binding of splicing factors to the corresponding binding sites. Although putative regulatory sites often overlap, no extensive study has examined whether overlapping regulatory sequences provide yet another dimension to splicing regulation. Here we analyzed experimentally-identified splicing regulatory sequences using a computational method based on the natural distribution of nucleotides and splicing regulatory sequences. We uncovered positive and negative interplay between overlapping regulatory sequences. Examination of these overlapping motifs revealed a unique spatial distribution, especially near splice donor sites of exons with weak splice donor sites. The positively selected overlapping splicing regulatory motifs were highly conserved among different species, implying functionality. Overall, these results suggest that overlap of two splicing regulatory binding sites is an evolutionary conserved widespread mechanism of splicing regulation. Finally,...Continue Reading

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Citations

Jun 19, 2012·Omics : a Journal of Integrative Biology·Mátyás CserhátiJános Györgyey
Nov 30, 2011·Omics : a Journal of Integrative Biology·Mátyás CserhátiJános Györgyey
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Sep 12, 2020·International Journal of Molecular Sciences·Tatiana KováčováLucie Grodecká

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