Abstract
Objective
MicroRNAs (miRNAs) play an important role in posttranscriptional regulation by binding to target sites in the 3′UTR of protein-coding genes. Genetic variation within target sites may potentially disrupt the binding activity of miRNAs, thereby impacting this regulation. In the current study, we investigated whether any established BMI-associated genetic variants potentially function by altering a miRNA target site.
Methods
The genomic positions of all predicted miRNA target site seed regions were identified, and these positions were queried in the T2D Knowledge Portal for variants that associated with BMI in the GIANT UK Biobank. This in silico analysis identified ten target site variants that associated with BMI with a P value ≤ 5 × 10−8. These ten variants mapped to nine genes, FAIM2, CCDC171, ADPGK, ZNF654, MLXIP, NT5C2, SHISA4, SLC25A22, and CTNNB1.
Results
In vitro functional analyses showed that five of these target site variants, rs7132908 (FAIM2), rs4963153 (SLC25A22), rs9460 (ADPGK), rs11191548 (NT5C2), and rs3008747 (CCDC171), disrupted the binding activity of miRNAs to their target in an allele-specific manner.
Conclusion
In conclusion, our study suggests that some established variants for BMI may function by altering miRNA binding to a 3′UTR target site.
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Acknowledgements
This study was funded by the Intramural Program of NIDDK, NIH.
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Kumar, P., Traurig, M. & Baier, L.J. Identification and functional validation of genetic variants in potential miRNA target sites of established BMI genes. Int J Obes 44, 1191–1195 (2020). https://doi.org/10.1038/s41366-019-0488-8
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DOI: https://doi.org/10.1038/s41366-019-0488-8