lin-4 and let-7 encode two small (21-25nt) RNAs that are required for the coordination of developmental timing in Co elegans. Both are temporally expressed and function as translational repressors by binding to complementary sequences found in the 3' UTRs of target RNAs. It has recently been discovered that these small RNAs represent the founding members of a new class of evolutionarily-conserved genes, termed microRNAs. At the present time, only two C. elegans RNA-binding proteins, ALG-1 and ALG-2, have been implicated in the processing and function of l/n-4 and let-7 RNAs. Experiments outlined in this proposal will elucidate the relationship between ALG-1/ALG-2 and lin-4, let-7 and other microRNAs. Specifically, a high-throughput RNAi screen will be employed to identify other C. elegans genes that require alg-1/alg-2 for function and will determine other regulatory/developmental pathways that require alg-1/alg-2 for efficient regulation. This genetic strategy will be complemented with molecular/biochemical techniques to identify additional microRNAs that require alg-1/alg-2 for processing and other proteins/RNAs that associate with the ALG-1/ALG-2 ribonucleoprotein complex.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM069186-03
Application #
6892822
Study Section
Special Emphasis Panel (ZRG1-F05 (20))
Program Officer
Portnoy, Matthew
Project Start
2003-06-02
Project End
2006-06-01
Budget Start
2005-06-02
Budget End
2006-06-01
Support Year
3
Fiscal Year
2005
Total Cost
$49,928
Indirect Cost
Name
Dartmouth College
Department
Genetics
Type
Schools of Medicine
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
Hammell, Christopher M; Lubin, Isabella; Boag, Peter R et al. (2009) nhl-2 Modulates microRNA activity in Caenorhabditis elegans. Cell 136:926-38
Hammell, Christopher M; Karp, Xantha; Ambros, Victor (2009) A feedback circuit involving let-7-family miRNAs and DAF-12 integrates environmental signals and developmental timing in Caenorhabditis elegans. Proc Natl Acad Sci U S A 106:18668-73
Lee, Rosalind C; Hammell, Christopher M; Ambros, Victor (2006) Interacting endogenous and exogenous RNAi pathways in Caenorhabditis elegans. RNA 12:589-97