dc.contributor.author | Nguyen, Thong T. | |
dc.contributor.author | Seoighe, Cathal | |
dc.date.accessioned | 2018-09-20T16:19:15Z | |
dc.date.available | 2018-09-20T16:19:15Z | |
dc.date.issued | 2013-11-18 | |
dc.identifier.citation | Nguyen, Thong T. Seoighe, Cathal (2013). Integrative analysis of mrna expression and half-life data reveals trans-acting genetic variants associated with increased expression of stable transcripts. PLoS ONE 8 (11), | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/10379/13117 | |
dc.description.abstract | Genetic variation in gene expression makes an important contribution to phenotypic variation and susceptibility to disease. Recently, a subset of cis-acting expression quantitative loci (eQTLs) has been found to result from polymorphisms that affect RNA stability. Here we carried out a search for trans-acting variants that influence RNA stability. We first demonstrate that differences in the activity of trans-acting factors that stabilize RNA can be detected by comparing the expression levels of long-lived (stable) and short-lived (unstable) transcripts in high-throughput gene expression experiments. Using gene expression microarray data generated from eight HapMap3 populations, we calculated the relative expression ranks of long-lived transcripts versus short-lived transcripts in each sample. Treating this as a quantitative trait, we applied genome-wide association and identified a single nucleotide polymorphism (SNP), rs6137010, on chromosome 20p13 with which it is strongly associated in two Asian populations (p=4x10(-10) in CHB - Han Chinese from Beijing; p=1x10(-4) in JPT - Japanese from Tokyo). This SNP is a cis-eQTL for SNRPB in CHB and JPT but not in the other six HapMap3 populations. SNRPB is a core component of the spliceosome, and has previously been shown to affect the expression of many RNA processing factors. We propose that a cis-eQTL of SNRPB may be directly responsible for inter-individual variation in relative expression of long-lived versus short-lived transcript in Asian populations. In support of this hypothesis, knockdown of SNRPB results in a significant reduction in the relative expression of long-lived versus short-lived transcripts. Samples with higher relative expression of long-lived transcripts also had higher relative expression of coding compared to non-coding RNA and of RNA from housekeeping compared to non-housekeeping genes, due to the lower decay rates of coding RNAs, particularly those that perform housekeeping functions, compared to non-coding RNAs. | |
dc.publisher | Public Library of Science (PLoS) | |
dc.relation.ispartof | PLoS ONE | |
dc.rights | Attribution-NonCommercial-NoDerivs 3.0 Ireland | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/3.0/ie/ | |
dc.subject | genome-wide analysis | |
dc.subject | posttranscriptional control | |
dc.subject | binding proteins | |
dc.subject | mammalian-cells | |
dc.subject | decay-rates | |
dc.subject | stability | |
dc.subject | elements | |
dc.subject | quantification | |
dc.subject | discovery | |
dc.subject | common | |
dc.title | Integrative analysis of mrna expression and half-life data reveals trans-acting genetic variants associated with increased expression of stable transcripts | |
dc.type | Article | |
dc.identifier.doi | 10.1371/journal.pone.0079627 | |
dc.local.publishedsource | http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0079627&type=printable | |
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