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Overlapping splicing regulatory motifs—combinatorial effects on splicing

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 fa...

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Autores principales: Goren, Amir, Kim, Eddo, Amit, Maayan, Vaknin, Keren, Kfir, Nir, Ram, Oren, Ast, Gil
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2010
Materias:
RNA
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2879502/
https://www.ncbi.nlm.nih.gov/pubmed/20110253
http://dx.doi.org/10.1093/nar/gkq005
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author Goren, Amir
Kim, Eddo
Amit, Maayan
Vaknin, Keren
Kfir, Nir
Ram, Oren
Ast, Gil
author_facet Goren, Amir
Kim, Eddo
Amit, Maayan
Vaknin, Keren
Kfir, Nir
Ram, Oren
Ast, Gil
author_sort Goren, Amir
collection PubMed
description 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, over-abundant motif overlaps were experimentally tested in a reporting minigene revealing that overlaps may facilitate a mode of splicing that did not occur in the presence of only one of the two regulatory sequences that comprise it.
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spelling pubmed-28795022010-06-02 Overlapping splicing regulatory motifs—combinatorial effects on splicing Goren, Amir Kim, Eddo Amit, Maayan Vaknin, Keren Kfir, Nir Ram, Oren Ast, Gil Nucleic Acids Res RNA 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, over-abundant motif overlaps were experimentally tested in a reporting minigene revealing that overlaps may facilitate a mode of splicing that did not occur in the presence of only one of the two regulatory sequences that comprise it. Oxford University Press 2010-06 2010-01-27 /pmc/articles/PMC2879502/ /pubmed/20110253 http://dx.doi.org/10.1093/nar/gkq005 Text en © The Author(s) 2010. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/2.5 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle RNA
Goren, Amir
Kim, Eddo
Amit, Maayan
Vaknin, Keren
Kfir, Nir
Ram, Oren
Ast, Gil
Overlapping splicing regulatory motifs—combinatorial effects on splicing
title Overlapping splicing regulatory motifs—combinatorial effects on splicing
title_full Overlapping splicing regulatory motifs—combinatorial effects on splicing
title_fullStr Overlapping splicing regulatory motifs—combinatorial effects on splicing
title_full_unstemmed Overlapping splicing regulatory motifs—combinatorial effects on splicing
title_short Overlapping splicing regulatory motifs—combinatorial effects on splicing
title_sort overlapping splicing regulatory motifs—combinatorial effects on splicing
topic RNA
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2879502/
https://www.ncbi.nlm.nih.gov/pubmed/20110253
http://dx.doi.org/10.1093/nar/gkq005
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