In the preceding grant period, we have identified two genes that are essential for meiosis in Drosophila oocytes, and that influence the translational activation of maternal mRNAs. Drosophila offers a very attractive system to study this regulatory pathway, since we can use both genetics and biochemistry to explore the molecules involved. We therefore propose to use a combined genetic and biochemical approach to analyze the meiotic cell cycle and translational activation in Drosophila oocytes/embryos: 1. Oocytes from females homozygous for either a grauzone or cortex mutation do not complete meiosis, and the embryos have defects in translational activation of certain maternal mRNAs. These results indicate that grauzone and cortex function in the meiotic cell cycle and translational regulation pathways. We will clone and characterize the grauzone and cortex genes, and explore their function during meiosis, oocyte maturation, and early development. 2. Translational activation of many maternal mRNas is controlled by cytoplasmic polyadenylation. This polyadenylation is regulated by proteins that interact with the 3' UTR of the mRNAs. We will characterize the transacting factors that bind to the 3' UTR of translationally activated Drosophila mRNAs, and determine the role of these proteins in regulating poly (A) tail length. Our strategy will include both a biochemical and a genetic approach for isolating the factors. These studies should identify key regulatory features of translation activation during development. These two aims are intimately linked. It is possible that either grauzone or cortex regulates the activity or expression of factors that bind to the 3' UTR of maternal mRNAs and regulate their translation. It is also possible that one of the 3' UTR binding factors is grauzone or cortex. We are confident that attacking the problem on both fronts will yield interesting new information about the meiotic cell cycle and how translational control participates in its regulation.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
7R01GM051584-06
Application #
6151062
Study Section
Molecular Biology Study Section (MBY)
Program Officer
Greenberg, Judith H
Project Start
1994-08-01
Project End
2003-08-31
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
6
Fiscal Year
2000
Total Cost
$342,719
Indirect Cost
Name
Rockefeller University
Department
Biology
Type
Other Domestic Higher Education
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065