Alternative polyadenylation mediates genetic regulation of gene expression.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32584258.
- Also identified by DOI 10.7554/eLife.57492 and PMC identifier 7338057.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Little is known about co-transcriptional or post-transcriptional regulatory mechanisms linking noncoding variation to variation in organismal traits. To begin addressing this gap, we used 3' Seq to study the impact of genetic variation on alternative polyadenylation (APA) in the nuclear and total mRNA fractions of 52 HapMap Yoruba human lymphoblastoid cell lines. We mapped 602 APA quantitative trait loci (apaQTLs) at 10% FDR, of which 152 were nuclear specific. Effect sizes at intronic apaQTLs are negatively correlated with eQTL effect sizes. These observations suggest genetic variants can decrease mRNA expression levels by increasing usage of intronic PAS. We also identified 24 apaQTLs associated with protein levels, but not mRNA expression. Finally, we found that 19% of apaQTLs can be associated with disease. Thus, our work demonstrates that APA links genetic variation to variation in gene expression, protein expression, and disease risk, and reveals uncharted modes of genetic regulation.
Medical subject headings
- Gene Expression Regulation
- Polyadenylation