RNA-binding proteins regulate aldosterone homeostasis in human steroidogenic cells

AngiotensinII (AngII) binds to the type I angiotensin receptor in the adrenal cortex to initiate a cascade of events leading to the production of aldosterone, a master regulator of blood pressure and volume. While the key signaling pathways, transcription factors, and steroidogenic enzymes necessary for adrenocortical production have been identified, surprisingly little is known about post-transcriptional regulation of this process. To investigate this question, we performed a high-resolution RNA-seq time course of the AngII stimulation response in a steroidogenic human cell line (H295R). We identified twelve temporally distinct groups of gene expression responses important for various steps of aldosterone production. AngII response kinetics for many of these mRNAs revealed a coordinated increase in both synthesis and decay. These findings were validated in primary human adrenocortical cells stimulated ex vivo with AngII or ACTH. RNA sequencing of AngII-treated H295R cells and AngII/ACTH-treated primary adrenocortical cells