RNA Regulatory Control of Human Steroidogenesis
Pr Neelanjan MUKHERJEE
University of Colorado, Anschutz School of Medicine, Aurora, USA
Monday, August 26th 2019 - 11 a.m.
- Auditorium, IGBMC
Hosted by Bertrand SERAPHIN
Human steroid hormones produced by the adrenal cortex control important physiology including metabolism, inflammation, blood pressure/volume, and sexual characteristics. Many human disorders are caused by the lack or excess of adrenal hormones. For example, 1 in 20 Americans suffer from high blood pressure caused by excessive adrenal aldosterone production. While the signaling components, transcriptional regulators, and steroidogenic enzymes necessary for production of hormones have been identified, little is known about post-transcriptional regulation of steroidogenesis by RNA-binding proteins (RBPs). Recently technological advances have revolutionized our ability to investigate RBP-driven RNA regulation, making it possible for the first time to investigate how these mechanisms contribute to steroidogenesis. We have recently carried out a screen for RBPs regulating human aldosterone production that revealed numerous RBPs. Many of these RBPs are regulators of cytoplasmic RNA stability and translation. Moreover, our transcriptome-wide approaches to study steroidogenic stimulus induced RNA expression kinetics indicate that mRNA stability controls the temporal pattern of RNA expression during steroidogenesis. Our current projects focus on understanding the molecular mechanisms, dynamics, and key regulatory interactions of these ribonucleoprotein complexes. Finally, the adrenal cortex is amenable to the delivery of modified oligonucleotides; thus, our discoveries may ultimately facilitate the design of oligonucleotide therapeutics that can be used to precisely and specifically modulate steroidogenesis through RBP-RNA disruption.