MicroRNAs belong to a novel class of gene regulatory molecules found in plants and animals that control gene expression by binding to complimentary sequences on target mRNAs. Hundreds of miRNAs have recently been identified in worm, fly, and mammalian genomes. The function of only five miRNAs has been elucidated in animals and all five control important developmental processes. The uncharacterized miRNAs may also act as important gene regulators during development. Thirty C. elegans miRNAs are temporally regulated during development, eleven of which share homology to mammalian miRNAs. The hypothesis to be tested is that conserved temporally expressed miRNAs essential for C. elegans development will also be important during mammalian development. This proposal will 1) characterize the expression patterns of six novel conserved and temporally regulated miRNAs in C. elegans 2) determine the role of select conserved and temporally regulated miRNAs during C. elegans development and 3) investigate the function of one or two promising temporally regulated miRNA homologues in the mouse. These studies will contribute to the understanding of gene regulation and development and may lead to valuable insights on human disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM071157-02
Application #
6909052
Study Section
Special Emphasis Panel (ZRG1-F05 (20))
Program Officer
Dearolf, Charles R
Project Start
2004-07-01
Project End
2007-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
2
Fiscal Year
2005
Total Cost
$48,296
Indirect Cost
Name
Yale University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Kato, M; Paranjape, T; Müller, R U et al. (2009) The mir-34 microRNA is required for the DNA damage response in vivo in C. elegans and in vitro in human breast cancer cells. Oncogene 28:2419-24
Esquela-Kerscher, Aurora; Trang, Phong; Wiggins, Jason F et al. (2008) The let-7 microRNA reduces tumor growth in mouse models of lung cancer. Cell Cycle 7:759-64
Johnson, Charles D; Esquela-Kerscher, Aurora; Stefani, Giovanni et al. (2007) The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res 67:7713-22
Schulman, Betsy R Maller; Esquela-Kerscher, Aurora; Slack, Frank J (2005) Reciprocal expression of lin-41 and the microRNAs let-7 and mir-125 during mouse embryogenesis. Dev Dyn 234:1046-54