Browsing by Subject "RNA stability"

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    Open Access
    Integrative analysis of mRNA expression and half-life data reveals trans-acting genetic variants associated with increased expression of stable transcripts
    (Public Library of Science, 2013) Nguyen, Thong T; Seoighe, Cathal
    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.