dc.contributor.author | Thomas, Laurent | |
dc.contributor.author | Sætrom, Pål | |
dc.date.accessioned | 2017-11-29T07:42:28Z | |
dc.date.available | 2017-11-29T07:42:28Z | |
dc.date.created | 2012-11-20T12:32:16Z | |
dc.date.issued | 2012 | |
dc.identifier.citation | PloS Computational Biology. 2012, 8 (8), . | nb_NO |
dc.identifier.issn | 1553-734X | |
dc.identifier.uri | http://hdl.handle.net/11250/2468317 | |
dc.description.abstract | Alternative polyadenylation (APA) can for example occur when a protein-coding gene has several polyadenylation (polyA) signals in its last exon, resulting in messenger RNAs (mRNAs) with different 3′ untranslated region (UTR) lengths. Different 3′UTR lengths can give different microRNA (miRNA) regulation such that shortened transcripts have increased expression. The APA process is part of human cells' natural regulatory processes, but APA also seems to play an important role in many human diseases. Although altered APA in disease can have many causes, we reasoned that mutations in DNA elements that are important for the polyA process, such as the polyA signal and the downstream GU-rich region, can be one important mechanism. To test this hypothesis, we identified single nucleotide polymorphisms (SNPs) that can create or disrupt APA signals (APA-SNPs). By using a data-integrative approach, we show that APA-SNPs can affect 3′UTR length, miRNA regulation, and mRNA expression—both between homozygote individuals and within heterozygote individuals. Furthermore, we show that a significant fraction of the alleles that cause APA are strongly and positively linked with alleles found by genome-wide studies to be associated with disease. Our results confirm that APA-SNPs can give altered gene regulation and that APA alleles that give shortened transcripts and increased gene expression can be important hereditary causes for disease. | nb_NO |
dc.language.iso | eng | nb_NO |
dc.publisher | Public Library of Science | nb_NO |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | Single Nucleotide Polymorphisms Can Create Alternative Polyadenylation Signals and Affect Gene Expression through Loss of MicroRNA-Regulation | nb_NO |
dc.type | Journal article | nb_NO |
dc.type | Peer reviewed | nb_NO |
dc.description.version | publishedVersion | nb_NO |
dc.source.pagenumber | 12 | nb_NO |
dc.source.volume | 8 | nb_NO |
dc.source.journal | PloS Computational Biology | nb_NO |
dc.source.issue | 8 | nb_NO |
dc.identifier.doi | 10.1371/journal.pcbi.1002621 | |
dc.identifier.cristin | 963559 | |
dc.relation.project | Norges forskningsråd: 205316 | nb_NO |
dc.description.localcode | © 2012 Thomas, Sætrom. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | nb_NO |
cristin.unitcode | 194,65,15,0 | |
cristin.unitcode | 194,63,10,0 | |
cristin.unitname | Institutt for klinisk og molekylær medisin | |
cristin.unitname | Institutt for datateknologi og informatikk | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |