Regulation of microRNA-375 by cAMP in pancreatic-βcells

David M. Keller, Elizabeth A. Clark, Richard H. Goodman

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

MicroRNA-375 (miR-375) is necessary for proper formation of pancreatic islets in vertebrates and is necessary for the development of β-cells in mice, but regulation of miR-375 in these cells is poorly understood. Here, we show that miR-375 is transcriptionally repressed by the cAMP-protein kinase A (PKA) pathway and that this repression is mediated through a block in RNA polymerase II binding to the miR-375 promoter. cAMP analogs that are PKA selective repress miR-375, as do cAMP agonists and the glucagon-like peptide-1 receptor agonist, exendin-4. Repression of the miR-375 precursor occurs rapidly in rat insulinoma INS-1 832/13 cells, within 15 min after cAMP stimulation, although the mature microRNA declines more slowly due to the kinetics of RNA processing. Repression of miR-375 in isolated rat islets by exendin-4 also occurs slowly, after several hours of stimulation. Glucose is another reported antagonist of miR-375 expression, although we demonstrate here that glucose does not target the microRNA through the PKA pathway. As reported previously, miR-375 negatively regulates insulin secretion, and attenuation of miR-375 through the cAMP-PKA pathway may boost the insulin response in pancreatic β-cells.

Original languageEnglish (US)
Pages (from-to)989-999
Number of pages11
JournalMolecular Endocrinology
Volume26
Issue number6
DOIs
StatePublished - Jun 1 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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