Integrative analysis of mRNA expression and half-life data reveals trans-acting genetic variants associated with increased expression of stable transcripts

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dc.contributor.authorNguyen, Thong Ten_ZA
dc.contributor.authorSeoighe, Cathalen_ZA
dc.date.accessioned2015-11-18T07:07:00Z
dc.date.available2015-11-18T07:07:00Z
dc.date.issued2013en_ZA
dc.description.abstractGenetic 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 =  4×10 −10 in CHB - Han Chinese from Beijing; p  = 1×10 −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.en_ZA
dc.identifier.apacitationNguyen, T. T., & Seoighe, C. (2013). Integrative analysis of mRNA expression and half-life data reveals trans-acting genetic variants associated with increased expression of stable transcripts. <i>PLoS One</i>, http://hdl.handle.net/11427/15123en_ZA
dc.identifier.chicagocitationNguyen, Thong T, and Cathal Seoighe "Integrative analysis of mRNA expression and half-life data reveals trans-acting genetic variants associated with increased expression of stable transcripts." <i>PLoS One</i> (2013) http://hdl.handle.net/11427/15123en_ZA
dc.identifier.citationNguyen, T. T., & Seoighe, C. (2012). 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), e79627. doi:10.1371/journal.pone.0079627en_ZA
dc.identifier.ris TY - Journal Article AU - Nguyen, Thong T AU - Seoighe, Cathal AB - 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 =  4×10 −10 in CHB - Han Chinese from Beijing; p  = 1×10 −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. DA - 2013 DB - OpenUCT DO - 10.1371/journal.pone.0079627 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2013 T1 - Integrative analysis of mRNA expression and half-life data reveals trans-acting genetic variants associated with increased expression of stable transcripts TI - Integrative analysis of mRNA expression and half-life data reveals trans-acting genetic variants associated with increased expression of stable transcripts UR - http://hdl.handle.net/11427/15123 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15123
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0079627
dc.identifier.vancouvercitationNguyen TT, Seoighe C. Integrative analysis of mRNA expression and half-life data reveals trans-acting genetic variants associated with increased expression of stable transcripts. PLoS One. 2013; http://hdl.handle.net/11427/15123.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis 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.en_ZA
dc.rights.holder© 2013 Nguyen, Seoigheen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherGene expressionen_ZA
dc.subject.otherRNA stabilityen_ZA
dc.subject.otherGenome-wide association studiesen_ZA
dc.subject.otherRNA processingen_ZA
dc.subject.otherPermutationen_ZA
dc.subject.otherRibonucleoproteinsen_ZA
dc.subject.otherGenetic locien_ZA
dc.subject.otherRNA structureen_ZA
dc.titleIntegrative analysis of mRNA expression and half-life data reveals trans-acting genetic variants associated with increased expression of stable transcriptsen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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