In the previous funding period, we identified about 200 genes that act as protein coding cofactors for the function of miRNAs and siRNAs in C. elegans. Some of these proteins were identified in genetic screens for decrease in miRNA function, some in genetic screens for decrease in siRNA function, and some in genetic screens for increase in siRNA function. We propose to dissect in detail how these proteins orchestrate the production, trafficking, and function of small RNAs in both mRNA degradation, mRNA translational control, and control of gene expression. We also propose to discern how the miRNA and siRNA and other small RNA pathways may compete with each other for common cofactors, thus leading to an increase in function in one pathway, when the other pathways is debilitated. The genes identified in this study are likely to be key factors in the function of small RNAs in biology and thus their identification may enable more potent RNAi based drug development. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM044619-17
Application #
7523342
Study Section
Molecular Genetics B Study Section (MGB)
Program Officer
Bender, Michael T
Project Start
1991-05-01
Project End
2012-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
17
Fiscal Year
2008
Total Cost
$633,121
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
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Tabach, Yuval; Golan, Tamar; Hernández-Hernández, Abrahan et al. (2013) Human disease locus discovery and mapping to molecular pathways through phylogenetic profiling. Mol Syst Biol 9:692

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