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Publication : Identification of regulatory elements directing miR-23a-miR-27a-miR-24-2 transcriptional regulation in response to muscle hypertrophic stimuli.

First Author  Hernandez-Torres F Year  2014
Journal  Biochim Biophys Acta Volume  1839
Issue  9 Pages  885-97
PubMed ID  25050919 Mgi Jnum  J:218483
Mgi Id  MGI:5617667 Doi  10.1016/j.bbagrm.2014.07.009
Citation  Hernandez-Torres F, et al. (2014) Identification of regulatory elements directing miR-23a-miR-27a-miR-24-2 transcriptional regulation in response to muscle hypertrophic stimuli. Biochim Biophys Acta 1839(9):885-97
abstractText  MiRNAs are small non-coding RNAs that significantly regulate the translation of protein coding genes in higher organisms. MicroRNAs are involved in almost every biological process, including early development, lineage commitment, growth and differentiation, cell death, and metabolic control. Misregulation of miRNAs belonging to the intergenic miR-23a-miR-27a-miR-24-2 cluster has been recently associated to cardiac and skeletal muscle diseases, and they are up-regulated in hypertrophic cardiomyopathy and skeletal muscle atrophy. Despite these facts, the basal transcriptional regulation of miR-23a/miR-27-a/miR-24-2 cluster and how it is altered under pathological conditions remain unclear. In this study, we identified and functionally characterized conserved upstream and downstream regulatory sequences from the miR-23a-miR-27a-miR-24-2 locus that are implicated on its transcriptional control. Our data demonstrate that Srf plays a pivotal role in modulating miR-23a-miR-27a-miR-24-2 cluster proximal promoter activity. Importantly, pro-hypertrophic signalling pathways such as those driven by angiotensin II and norepinephrine also regulate miR-23a-miR-27a-miR-24-2 cluster proximal promoter activity. Taking together, our results provide new insights into the regulatory networks driving miR-23a-miR-27a-miR-24-2 cluster expression in cardiac and skeletal muscles.
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