MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus, Oxfordshire OX11 0RD, UK.
Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands; Big Data Institute, Li Ka Shing Center for Health Information and Discovery, Oxford University, Oxford, UK; Program in Medical Population Genetics, Broad Institute, Cambridge, MA, USA.
Biochim Biophys Acta Gene Regul Mech. 2020 Nov;1863(11):194640. doi: 10.1016/j.bbagrm.2020.194640. Epub 2020 Sep 30.
We have prioritised a single nucleotide polymorphism (SNP) rs2645294 as one candidate functional SNP in the TBX15-WARS2 waist-hip-ratio locus using posterior probability analysis. This SNP is located in the 3' untranslated region of the WARS2 (tryptophanyl tRNA synthetase 2, mitochondrial) gene with which it has an expression quantitative trait in subcutaneous white adipose tissue. We show that transcripts of the WARS2 gene in a human white adipose cell line, heterozygous for the rs2645294 SNP, showed allelic imbalance. We tested whether the rs2645294 SNP altered WARS2 RNA stability using three different methods: actinomycin-D inhibition and RNA decay, mature and nascent RNA analysis and luciferase reporter assays. We found no evidence of a difference in RNA stability between the rs2645294 alleles indicating that the allelic expression imbalance was likely due to transcriptional regulation.
我们使用后验概率分析，将单核苷酸多态性 (SNP) rs2645294 确定为 TBX15-WARS2 腰围-臀围比值基因座中的一个候选功能 SNP。该 SNP 位于 WARS2（色氨酰 tRNA 合成酶 2，线粒体）基因的 3'非翻译区，与它在皮下白色脂肪组织中有表达数量性状。我们表明，在人白色脂肪细胞系中，rs2645294 SNP 杂合子的 WARS2 基因转录本表现出等位基因不平衡。我们使用三种不同的方法测试了 rs2645294 SNP 是否改变了 WARS2 RNA 的稳定性：放线菌素-D 抑制和 RNA 衰减、成熟和新生 RNA 分析以及荧光素酶报告基因测定。我们没有发现 rs2645294 等位基因之间 RNA 稳定性存在差异的证据，这表明等位基因表达不平衡可能是由于转录调控所致。
