MicroRNAs (or miRNAs) are non-coding RNAs that are believed to act by incomplete base pairing with the 3'-untranslated region of target mRNAs leading to post-transcriptional gene silencing. We have identified novel miRNAs specific to the pancreatic islet. The miRNAs are conserved in mouse and human, suggesting a role in endocrine pancreas specification, and possibly glucose-induced secretion. We propose a series of molecular genetic, biochemical and bioinformatics studies to elucidate the molecular function of islet miRNA.
In aim1, we will overexpress two novel islet-specific miRNAs in pancreatic beta cell lines and islets and study insulin secretion in response to a variety of insulin secretagogues. We will also inhibit miRNA function by transfecting 2'-O-methyl RNA oligonucleotides that are complimentary to the islet specific miRNAs.
In aim 2, we will complete the generation of a mutant mouse in which the most abundant islet-specific miRNA has been replaced by a gene encoding a red fluorescent protein (RFP) by targeted """"""""knock-in"""""""" and homologous recombination in ES cells.
In aim3, we propose to use bioinformatic tools that will help in the identification of miRNA targets. Predicted targets will be validated in cell lines (aim1) and pancreatic islets (aim2).

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK069012-02
Application #
7015585
Study Section
Special Emphasis Panel (ZRG1-F06 (20))
Program Officer
Hyde, James F
Project Start
2005-02-01
Project End
2006-12-31
Budget Start
2006-02-01
Budget End
2006-12-31
Support Year
2
Fiscal Year
2006
Total Cost
$46,516
Indirect Cost
Name
Rockefeller University
Department
Internal Medicine/Medicine
Type
Other Domestic Higher Education
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
Rosu, Simona; Cohen-Fix, Orna (2017) Live-imaging analysis of germ cell proliferation in the C. elegans adult supports a stochastic model for stem cell proliferation. Dev Biol 423:93-100
Yi, Rui; Poy, Matthew N; Stoffel, Markus et al. (2008) A skin microRNA promotes differentiation by repressing 'stemness'. Nature 452:225-9
Poy, M N; Spranger, M; Stoffel, M (2007) microRNAs and the regulation of glucose and lipid metabolism. Diabetes Obes Metab 9 Suppl 2:67-73