Stress hormones may silence crucial neuronal genes through specific RNA molecules, according to a study by researchers at the University of Alabama at Birmingham. The study, led by Professor Yogesh Dwivedi, reveals that long noncoding RNAs (lncRNAs) associate with the polycomb repressive complex 2 (PRC2) to modify chromatin following activation of the glucocorticoid receptor (GR), the cell's master regulator of stress response. This discovery provides a structural route by which stress hormones influence gene expression, reshaping the genome's architecture and silencing nearby genes, including those linked to synaptic function. The research challenges the notion that stress is solely adaptive or destructive, highlighting its complex impact on the brain and its potential to rewire neural pathways. The study's findings offer a novel perspective on the molecular mechanisms underlying stress-related disorders, such as major depressive disorder (MDD), and suggest that interventions targeting lncRNA-PRC2 interactions could reawaken silenced genes involved in neuroplasticity. The research team, affiliated with the Heersink School of Medicine, University of Alabama at Birmingham, emphasizes the importance of further investigation into the potential of lncRNAs as biomarkers for stress vulnerability and targets for next-generation antidepressants. The study's comprehensive approach, integrating transcriptomic, epigenomic, and genome-wide chromatin-level data, provides a clear mechanistic link between glucocorticoid signaling and durable transcriptional repression, offering insights into the broader landscape of psychiatric research and the role of basic molecular biology in understanding stress-related disorders.
