Genome-wide association between branch point properties and alternative splicing.

The branch point (BP) is one of the three obligatory signals required for pre-mRNA splicing. In mammals, the degeneracy of the motif combined with the lack of a large set of experimentally verified BPs complicates the task of modeling it in silico, and therefore of predicting the location of natural...

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Autores principales:	André Corvelo, Martina Hallegger, Christopher W J Smith, Eduardo Eyras
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c0e60278c15542e58e298e6ea04b5cdd
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spelling	oai:doaj.org-article:c0e60278c15542e58e298e6ea04b5cdd2021-11-18T05:51:53ZGenome-wide association between branch point properties and alternative splicing.1553-734X1553-735810.1371/journal.pcbi.1001016https://doaj.org/article/c0e60278c15542e58e298e6ea04b5cdd2010-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21124863/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The branch point (BP) is one of the three obligatory signals required for pre-mRNA splicing. In mammals, the degeneracy of the motif combined with the lack of a large set of experimentally verified BPs complicates the task of modeling it in silico, and therefore of predicting the location of natural BPs. Consequently, BPs have been disregarded in a considerable fraction of the genome-wide studies on the regulation of splicing in mammals. We present a new computational approach for mammalian BP prediction. Using sequence conservation and positional bias we obtained a set of motifs with good agreement with U2 snRNA binding stability. Using a Support Vector Machine algorithm, we created a model complemented with polypyrimidine tract features, which considerably improves the prediction accuracy over previously published methods. Applying our algorithm to human introns, we show that BP position is highly dependent on the presence of AG dinucleotides in the 3' end of introns, with distance to the 3' splice site and BP strength strongly correlating with alternative splicing. Furthermore, experimental BP mapping for five exons preceded by long AG-dinucleotide exclusion zones revealed that, for a given intron, more than one BP can be chosen throughout the course of splicing. Finally, the comparison between exons of different evolutionary ages and pseudo exons suggests a key role of the BP in the pathway of exon creation in human. Our computational and experimental analyses suggest that BP recognition is more flexible than previously assumed, and it appears highly dependent on the presence of downstream polypyrimidine tracts. The reported association between BP features and the splicing outcome suggests that this, so far disregarded but yet crucial, element buries information that can complement current acceptor site models.André CorveloMartina HalleggerChristopher W J SmithEduardo EyrasPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 6, Iss 11, p e1001016 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 André Corvelo Martina Hallegger Christopher W J Smith Eduardo Eyras Genome-wide association between branch point properties and alternative splicing.
description	The branch point (BP) is one of the three obligatory signals required for pre-mRNA splicing. In mammals, the degeneracy of the motif combined with the lack of a large set of experimentally verified BPs complicates the task of modeling it in silico, and therefore of predicting the location of natural BPs. Consequently, BPs have been disregarded in a considerable fraction of the genome-wide studies on the regulation of splicing in mammals. We present a new computational approach for mammalian BP prediction. Using sequence conservation and positional bias we obtained a set of motifs with good agreement with U2 snRNA binding stability. Using a Support Vector Machine algorithm, we created a model complemented with polypyrimidine tract features, which considerably improves the prediction accuracy over previously published methods. Applying our algorithm to human introns, we show that BP position is highly dependent on the presence of AG dinucleotides in the 3' end of introns, with distance to the 3' splice site and BP strength strongly correlating with alternative splicing. Furthermore, experimental BP mapping for five exons preceded by long AG-dinucleotide exclusion zones revealed that, for a given intron, more than one BP can be chosen throughout the course of splicing. Finally, the comparison between exons of different evolutionary ages and pseudo exons suggests a key role of the BP in the pathway of exon creation in human. Our computational and experimental analyses suggest that BP recognition is more flexible than previously assumed, and it appears highly dependent on the presence of downstream polypyrimidine tracts. The reported association between BP features and the splicing outcome suggests that this, so far disregarded but yet crucial, element buries information that can complement current acceptor site models.
format	article
author	André Corvelo Martina Hallegger Christopher W J Smith Eduardo Eyras
author_facet	André Corvelo Martina Hallegger Christopher W J Smith Eduardo Eyras
author_sort	André Corvelo
title	Genome-wide association between branch point properties and alternative splicing.
title_short	Genome-wide association between branch point properties and alternative splicing.
title_full	Genome-wide association between branch point properties and alternative splicing.
title_fullStr	Genome-wide association between branch point properties and alternative splicing.
title_full_unstemmed	Genome-wide association between branch point properties and alternative splicing.
title_sort	genome-wide association between branch point properties and alternative splicing.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/c0e60278c15542e58e298e6ea04b5cdd
work_keys_str_mv	AT andrecorvelo genomewideassociationbetweenbranchpointpropertiesandalternativesplicing AT martinahallegger genomewideassociationbetweenbranchpointpropertiesandalternativesplicing AT christopherwjsmith genomewideassociationbetweenbranchpointpropertiesandalternativesplicing AT eduardoeyras genomewideassociationbetweenbranchpointpropertiesandalternativesplicing
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Genome-wide association between branch point properties and alternative splicing.

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