The contribution of RNA decay quantitative trait loci to inter-individual variation in steady-state gene expression levels
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE37451 | GEO | 2012/10/01
SECONDARY ACCESSION(S): PRJNA160139
REPOSITORIES: GEO
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Project description:Analysis of the extent to which inter-individual variation in mRNA decay contributes to inter-individual variation in gene expression levels in humans. The study examines properties of genome-wide decay rates and the relationship between mRNA decay and gene expression across genes, across individuals, and finally across genotype classes. 70 human lymphoblastoid cell lines were treated with Actinomycin D to arrest transcription. Transcript abundance was measured at 5 timepoints: before transcription (0 hours) and after transcription (0.5 hours, 1 hour, 2 hours, and 4 hours). Data was then used to estimate gene-specific decay rates genome-wide.
2012-10-01 | E-GEOD-37451 | biostudies-arrayexpress
Project description:Recent gene expression QTL (eQTL) mapping studies have provided considerable insight into the genetic basis for inter-individual regulatory variation. However, a limitation of all eQTL studies to date, which have used measurements of steady-state gene expression levels, is the inability to directly distinguish between variation in transcription and decay rates. To address this gap, we performed a genome-wide study of variation in gene-specific mRNA decay rates across individuals. Using a time-course study design, we estimated mRNA decay rates for over 16,000 genes in 70 Yoruban HapMap lymphoblastoid cell lines (LCLs), for which extensive genotyping data are available. Considering mRNA decay rates across genes, we found that: (i) as expected, highly expressed genes are generally associated with lower mRNA decay rates, (ii) genes with rapid mRNA decay rates are enriched with putative binding sites for miRNA and RNA binding proteins, and (iii) genes with similar functional roles tend to exhibit correlated rates of mRNA decay. Focusing on variation in mRNA decay across individuals, we estimate that steady-state expression levels are significantly correlated with variation in decay rates in 10% of genes. Somewhat counter-intuitively, for about half of these genes, higher expression is associated with faster decay rates, possibly due to a coupling of mRNA decay with transcriptional processes in genes involved in rapid cellular responses. Finally, we used these data to map genetic variation that is specifically associated with variation in mRNA decay rates across individuals. We found 195 such loci, which we named RNA decay quantitative trait loci ("rdQTLs"). All the observed rdQTLs are located near the regulated genes and therefore are assumed to act in cis. By analyzing our data within the context of known steady-state eQTLs, we estimate that a substantial fraction of eQTLs are associated with inter-individual variation in mRNA decay rates.
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2017-12-05 | GSE98747 | GEO
Project description:Fox BW, Ponomarova O, Lee YU, Zhang G, Giese EG, Walker M, Roberto NM, Na H, Reis-Rodrigues P, Curtis BJ, Kolodziej AR, Crombie TA, Zdraljevic S, Yilmaz LS, Andersen EC, Schroeder FC, Walhout AJM (2022) C. elegans as a model for inter-individual variation in metabolism
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Project description:Gene expression levels are determined by the balance between rates of mRNA transcription and decay, and genetic variation in either of these processes can result in heritable differences in transcript abundance. Although the genetics of gene expression has been the subject of intense interest, the contribution of heritable variation in mRNA decay rates to gene expression variation has received far less attention. To this end, we developed a novel statistical framework and measured allele-specific differences in mRNA decay rates in a diploid yeast hybrid created by mating two genetically diverse parental strains. In total, we estimate that 31% of genes exhibit allelic differences in mRNA decay rate, of which 350 can be identified at a false discovery rate of 10%. Genes with significant allele-specific differences in mRNA decay rate have higher levels of polymorphism compared to other genes, with all gene regions contributing to allelic differences in mRNA decay rate. Strikingly, we find widespread evidence for compensatory evolution, such that variants influencing transcriptional initiation and decay having opposite effects, suggesting steady-state gene expression levels are subject to pervasive stabilizing selection. Our results demonstrate that heritable differences in mRNA decay rates are widespread, and are an important target for natural selection to maintain or fine-tune steady-state gene expression levels.
2014-09-16 | GSE60617 | GEO
Project description:The genomic distribution of trait-associated SNPs (TASs) discovered in genome-wide association studies (GWAS) can provide insight into the genetic architecture of complex traits and the design of future studies. Here we report on a maize GWAS that identified TASs underlying five quantitative traits measured across a large panel of samples and examine the characteristics of these TASs. A set of SNPs obtained via RNA sequencing (RNA-seq), most of which are located within annotated genes (~87%) were complemented with additional SNPs from the maize HapMap Project that contains approximately equal proportions of intragenic and intergenic SNPs. TASs were identified via a genome scan while controlling for polygenic background effects. The diverse functions of TAS-containing candidate genes indicate that complex genetic networks shape these traits. The vast majority of the TAS-containing candidate genes have dynamic expression levels among developmental stages. Overall, TASs explain 44~54% of the total phenotypic variation for these traits, with equal contributions from intra- and inter-genic TASs. Association of ligueless2 with upper leaf angle was implicated by two intragenic TASs; rough sheath1 was associated with leaf width by an upstream intergenic TAS; and Zea agamous5 was associated with days to silking by both intra- and inter-genic TASs. A large proportion (82%) of these TASs comes from noncoding regions, similar to findings from human diseases and traits. However, TASs were enriched in both intergenic (53%) and promoter 5kb (24%) regions, but under-represented in a set of nonsynonymous SNPs.
2012-06-11 | E-MTAB-4233 | biostudies-arrayexpress
Project description:mRNA decay in E. Coli degradosome mutants and their parental strains following transcriptional arrest with rifampicin. Abstract: RNase E, an essential endoribonuclease of Escherichia coli, interacts through its C-terminal region with multiple other proteins to form a complex termed the RNA degradosome. To investigate the degradosome's proposed role as an RNA decay machine, we used DNA microarrays to globally assess alterations in the steady-state abundance and decay of 4,289 E. coli mRNAs at single-gene resolution in bacteria carrying mutations in the degradosome constituents RNase E, polynucleotide phosphorylase, RhlB helicase, and enolase. Our results show that the functions of all four of these proteins are necessary for normal mRNA turnover. We identified specific transcripts and functionally distinguishable transcript classes whose half-life and abundance were affected congruently by multiple degradosome proteins, affected differentially by mutations in degradosome constituents, or not detectably altered by degradosome mutations. Our results, which argue that decay of some E. coli mRNAs in vivo depends on the action of assembled degradosomes, whereas others are acted on by degradosome proteins functioning independently of the complex, imply the existence of structural features or biochemical factors that target specific classes of mRNAs for decay by degradosomes. An RNA stablity experiment design type examines stability and/or decay of RNA transcripts. User Defined
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