Our ultimate goal is to understand the mechanisms by which maternally stored molecules control the earliest stages of vertebrate development. In particular, we are interested in the mechanisms that control the translational activation of stored maternal mRNAs during oocyte maturation and embryonic development prior to zygotic transcription. The translation of many stored maternal mRNAs is activated when their 3' poly (A) tails are elongated in a specific and developmentally regulated poly (A) addition reaction that takes place in the cytoplasm. This application is concerned with the regulated addition of poly (A) tails to maternal mRNAs that occurs during projesterone-induced oocyte maturation of the frog, Xenopus laevis. Specifically, we propose that a novel poly (A) tail binding protein that we have identified and named embryonic PABII (ePABII) is required for the selective 3' poly (A) elongation of particular maternal mRNAs during oocyte maturation. The developmental expression pattern of ePABII and its cytoplasmic location provide compelling circumstantial evidence that ePABII is involved in the dynamic mRNA poly (A) tail changes that occur during oocyte maturation and the maternal stages of development. This RO3 application describes several types of experiments designed to test directly the potential functional role of ePABII in maturation-specific mRNA poly (A) tail changes. Data from these initial experiments will provide the preliminary evidence critical for a more comprehensive RO1 grant that will focus on the mechanistic role of ePABII in the maternally controlled development of Xenopus laevis and other vertebrates. ? ?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
5R03HD044049-02
Application #
6723751
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Tasca, Richard J
Project Start
2003-06-01
Project End
2005-05-31
Budget Start
2004-06-01
Budget End
2005-05-31
Support Year
2
Fiscal Year
2004
Total Cost
$70,475
Indirect Cost
Name
University of Wisconsin Madison
Department
Biochemistry
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Song, Jikui; McGivern, Jered V; Nichols, Karl W et al. (2008) Structural basis for RNA recognition by a type II poly(A)-binding protein. Proc Natl Acad Sci U S A 105:15317-22
Good, Peter J; Abler, Lisa; Herring, Dina et al. (2004) Xenopus embryonic poly(A) binding protein 2 (ePABP2) defines a new family of cytoplasmic poly(A) binding proteins expressed during the early stages of vertebrate development. Genesis 38:166-75