Journal article
miRNAs control insulin content in pancreatic beta-cells via downregulation of transcriptional repressors
EMBO Journal, Vol.30(5), pp.835-845
Mar/2011
Abstract
MicroRNAs (miRNAs) were shown to be important for pancreas development, yet their roles in differentiated beta-cells remain unclear. Here, we show that miRNA inactivation in beta-cells of adult mice results in a striking diabetic phenotype. While islet architecture is intact and differentiation markers are maintained, Dicer1-deficient beta-cells show a dramatic decrease in insulin content and insulin mRNA. As a consequence of the change in insulin content, the animals become diabetic. We provide evidence for involvement of a set of miRNAs in regulating insulin synthesis. The specific knockdown of miR-24, miR-26, miR-182 or miR-148 in cultured beta-cells or in isolated primary islets downregulates insulin promoter activity and insulin mRNA levels. Further, miRNA-dependent regulation of insulin expression is associated with upregulation of transcriptional repressors, including Bhlhe22 and Sox6. Thus, miRNAs in the adult pancreas act in a new network that reinforces insulin expression by reducing the expression of insulin transcriptional repressors. The EMBO Journal (2011) 30, 835-845. doi: 10.1038/emboj.2010.361; Published online 1 February 2011
Details
- Title
- miRNAs control insulin content in pancreatic beta-cells via downregulation of transcriptional repressors
- Creators
- Tal Melkman-Zehavi (null)Roni Oren (null) - The Weizmann Institute of ScienceSharon Kredo-Russo (null) - 972WIS_INST___111Tirosh Shapira (null) - 972WIS_INST___122Amitai D. Mandelbaum (null)Natalia Rivkin (null) - The Weizmann Institute of ScienceTomer Nir (null)Kim A. Lennox (null)Mark A. Behlke (null)Yuval Dor (null)Eran Hornstein (null) - 972WIS_INST___111
- Resource Type
- Journal article
- Publication Details
- EMBO Journal, Vol.30(5), pp.835-845; Mar/2011
- Number of pages
- 11
- Language
- English
- DOI
- https://doi.org/10.1038/emboj.2010.361
- Grant note
- Juvenile Diabetes Research Foundation [99-2007-71]; EFSD/D-Cure Young Investigator award; Israel Science Foundation; Yeda-Sela Center for Basic Research; Wolfson Family Charitable Trust; Israeli Immigration department; JDRF; Helmsley foundation; EU [241883]We thank Chris Wright for the rabbit anti-Pdx1 antibody. Corrinne Lobe for the ZE/G allele, Brain Harfe, Mike McManus and Cliff Tabin for the Dicer1 conditional allele, Doug Melton for the RIP-CreER allele. We thank Mike Walker Shimon Efrat and Yehiel Zick for discussions. This work was supported by grants to EH from Juvenile Diabetes Research Foundation (#99-2007-71), the EFSD/D-Cure Young Investigator award, the Israel Science Foundation, the Yeda-Sela Center for Basic Research and the Wolfson Family Charitable Trust. EH is the incumbent of the Helen and Milton A Kimmelman Career Development Chair. TMZ was partially supported by a grant from the Israeli Immigration department. YD is funded by JDRF, the Helmsley foundation and EU FP7 (# 241883)._ALMAME_DELIMITER_
- Record Identifier
- 993268029603596
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