ArticlePloS one2013
A polymorphic 3'UTR element in ATP1B1 regulates alternative polyadenylation and is associated with blood pressure.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 18 citations in OpenAlex.
- Alternative polyadenylation regulation in cardiac development and cardiovascular disease.Cardiovascular research · 2023Review
- Postnatal nutrition environment reprograms renal DNA methylation patterns in offspring of maternal protein-restricted stroke-prone spontaneously hypertensive rats.Frontiers in nutrition · 2023Article
- An atlas of alternative polyadenylation quantitative trait loci contributing to complex trait and disease heritability.Nature genetics · 2021Article
- Systematic identification of functional SNPs interrupting 3'UTR polyadenylation signals.PLoS genetics · 2020Article
- Emerging Roles of RNA 3'-end Cleavage and Polyadenylation in Pathogenesis, Diagnosis and Therapy of Human Disorders.Biomolecules · 2020Review
- A compendium of conserved cleavage and polyadenylation events in mammalian genes.Genome research · 2018Article
- Alternative polyadenylation of mRNA precursors.Nature reviews. Molecular cell biology · 2017Review
- Principles of miRNA-mRNA interactions: beyond sequence complementarity.Cellular and molecular life sciences : CMLS · 2015Review
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
Although variants in many genes have previously been shown to be associated with blood pressure (BP) levels, the molecular mechanism underlying these associations are mostly unknown. We identified a multi-allelic T-rich sequence (TRS) in the 3'UTR of ATP1B1 that varies in length and sequence composition (T22-27 and T12GT 3GT6). The 3'UTR of ATP1B1 contains 2 functional polyadenylation signals and the TRS is downstream of the proximal polyadenylation site (A2). Therefore, we hypothesized that alleles of this TRS might influence ATP1B1 expression by regulating alternative polyadenylation. In vitro, the T12GT 3GT6 allele increases polyadenylation at the A2 polyadenylation site as compared to the T23 allele. Consistent with our hypothesis, the relative abundance of the A2-polyadenylated ATP1B1 mRNA was higher in human kidneys with at least one copy of the T12GT 3GT6 allele than in those lacking this allele. The T12GT 3GT6 allele is also associated with higher systolic BP (beta = 3.3 mmHg, p = 0.014) and diastolic BP (beta = 2.4 mmHg, p = 0.003) in a European-American population. Therefore, we have identified a novel multi-allelic TRS in the 3'UTR of ATP1B1 that is associated with higher BP and may mediate its effect by regulating the polyadenylation of the ATP1B1 mRNA.
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Registered trials
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