Abstract
The regulation of mRNA stability has emerged as a critical control step in dynamic gene expression. This process occurs in response to modifications of the cellular environment, including hormonal variations, and regulates the expression of subsets of proteins whose levels need to be rapidly adjusted. Modulation of messenger RNA stability is usually mediated by stabilizing or destabilizing RNA-binding proteins (RNA-BP) that bind to the 3′-untranslated region regulatory motifs, such as AU-rich elements (AREs). Destabilizing ARE-binding proteins enhance the decay of their target transcripts by recruiting the mRNA decay machineries. Failure of such mechanisms, in particular misexpression of RNA-BP, has been linked to several human diseases. In the adrenal cortex, the expression and activity of mRNA stability regulatory proteins are still understudied. However, ACTH- or cAMP-elicited changes in the expression/phosphorylation status of the major mRNA-destabilizing protein TIS11b/BRF1 or in the subcellular localization of the stabilizing protein Human antigen R have been reported. They suggest that this level of regulation of gene expression is also important in endocrinology.
Highlights
Transcriptional regulation of the cellular responses to hormones has been the primary focus of many endocrinological research studies during the past decades
Through binding to its adenylate-cyclase-coupled receptor MC2R, ACTH stimulates the release of cAMP and the activation of the cAMP-dependent protein kinase A (PKA), which in turn phosphorylates and regulates a number of specific substrates including the steroidogenic acute regulatory protein (StAR) [1] and the cAMP response element-binding protein (CREB) [2]
ACTH strongly regulates the transcription of a number of genes involved in the Abbreviations: TIS11b, TPA-inducible sequence 11b; BRF1, butyrate response factor 1; ZFP36, zinc finger protein; TTP, tristetraprolin; CCR4, carbon catabolite repressor protein 4; CNOT1, CCR4-NOT transcription complex subunit 1; Dcp1a, decapping enzyme 1a
Summary
Edited by: Antoine Martinez, Centre National de la Recherche Scientifique (CNRS), France. Specialty section: This article was submitted to Neuroendocrine Science, a section of the journal
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