A lead candidate functional single nucleotide polymorphism within the WARS2 gene associated with waist-hip-ratio does not alter RNA stability.

Milan Mušo, Rebecca Dumbell, Sara Pulit, Nasa Sinnott-Armstrong, Samantha Laber, Louisa Zolkiewski, Liz Bentley, Melina Claussnitzer, Roger D Cox

Biochimica et biophysica acta. Gene regulatory mechanisms 2020 Nov

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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. Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.

Citation

Milan Mušo, Rebecca Dumbell, Sara Pulit, Nasa Sinnott-Armstrong, Samantha Laber, Louisa Zolkiewski, Liz Bentley, Melina Claussnitzer, Roger D Cox. A lead candidate functional single nucleotide polymorphism within the WARS2 gene associated with waist-hip-ratio does not alter RNA stability. Biochimica et biophysica acta. Gene regulatory mechanisms. 2020 Nov;1863(11):194640