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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.
Pubmed ID: 28163695 RIS Download
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Database that contains the complete entries of human ARE-containing full-length mRNAs.
ARED is further clustered into five groups depending on the number of motifs in the ARE stretch. Groups 1-4 contain five, four, three and two pentameric (AUUUA) repeats, respectively, while Group 5 contains only one repeat within the 13-bp pattern. Clustering was performed in such a way that, for example, Group 1 included not only exact five or more continuous ARE pentamers but also those with 10% ambiguity, so that a stretch of NUUUAUUUAUUUAUUUAUUUN would fall in this category. This process was verified by a phylogenic tree relationship using Clustal-W alignment of ARE stretches and their variations. As could be expected, this analysis showed that the lower the number of ARE motifs in a group, the higher the number of sequences that were included, and apparently the more functionally diverse the corresponding ARE-genes.
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