A Functional riboSNitch in the 3' Untranslated Region of FKBP5 Alters MicroRNA-320a Binding Efficiency and Mediates Vulnerability to Chronic Post-Traumatic Pain

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Sarah D LinnstaedtSamuel A McLean

Abstract

Previous studies have shown that common variants of the gene coding for FK506-binding protein 51 (FKBP5), a critical regulator of glucocorticoid sensitivity, affect vulnerability to stress-related disorders. In a previous report, FKBP5 rs1360780 was identified as a functional variant because of its effect on gene methylation. Here we report evidence for a novel functional FKBP5 allele, rs3800373. This study assessed the association between rs3800373 and post-traumatic chronic pain in 1607 women and men from two ethnically diverse human cohorts. The molecular mechanism through which rs3800373 affects adverse outcomes was established via in silico, in vivo, and in vitro analyses. The rs3800373 minor allele predicted worse adverse outcomes after trauma exposure, such that individuals with the minor (risk) allele developed more severe post-traumatic chronic musculoskeletal pain. Among these individuals, peritraumatic circulating FKBP5 expression levels increased as cortisol and glucocorticoid receptor (NR3C1) mRNA levels increased, consistent with increased glucocorticoid resistance. Bioinformatic, in vitro, and mutational analyses indicate that the rs3800373 minor allele reduces the binding of a stress- and pain-associated microRN...Continue Reading

Citations

Jan 24, 2019·Biomolecules·Andreas HähleFelix Hausch
Nov 30, 2019·Frontiers in Psychiatry·Shui JiangKatherine J Aitchison
Oct 7, 2020·Healthcare·Ivone Castro-Vale, Davide Carvalho
Feb 6, 2021·Stress : the International Journal on the Biology of Stress·Anja RichterOliver Gruber
Jan 19, 2021·European Journal of Pain : EJP·Francesca L BeaudoinUNKNOWN AURORA Study Group
Mar 6, 2021·Journal of Medicinal Chemistry·Michael BauderFelix Hausch
Apr 29, 2021·The Journal of International Medical Research·Zhenya GaoShijie Yao
Apr 13, 2021·Angewandte Chemie·Andreas M VollFelix Hausch
Jun 17, 2021·Journal of Affective Disorders·Xing-Xing ChenYing Sun

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