Establishment of polarity in the egg can be viewed as the earliest step in embryonic patterning. Thus, differences in cell fate among the early cleavage cells are a consequence of asymmetric distributions of informational molecules in the egg cytoplasm before fertilization. The basis for such polarity is provided by localized maternal determinants in the form of protein or mRNA. While there is evidence for the existence of localized determinants in many systems, the localization process is still poorly understood. This research proposal addresses this problem by investigating the biochemical mechanisms underlying mRNA localization, using the frog Xenopus laevis as a model. The PI has purified and cloned an essential localization factor, identified other proteins that are potential localization factors, and defined these critical sequences within an RNA localization signal. The following specific aims are proposed: (1) characterization of VgRBP60, the essential localization factor; (2) investigation of the mechanism of mRNA localization; (3) analysis of other RNA-protein interactions mediating localization, and purification and characterization of other protein components of the localization machinery.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD030699-08
Application #
6520920
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Program Officer
Tasca, Richard J
Project Start
1993-09-01
Project End
2004-04-30
Budget Start
2002-05-01
Budget End
2003-04-30
Support Year
8
Fiscal Year
2002
Total Cost
$259,342
Indirect Cost
Name
Brown University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912
King, Mary Lou; Messitt, Timothy J; Mowry, Kimberly L (2005) Putting RNAs in the right place at the right time: RNA localization in the frog oocyte. Biol Cell 97:19-33
Lewis, Raymond A; Kress, Tracy L; Cote, Colette A et al. (2004) Conserved and clustered RNA recognition sequences are a critical feature of signals directing RNA localization in Xenopus oocytes. Mech Dev 121:101-9
Chang, Patrick; Torres, Jan; Lewis, Raymond A et al. (2004) Localization of RNAs to the mitochondrial cloud in Xenopus oocytes through entrapment and association with endoplasmic reticulum. Mol Biol Cell 15:4669-81
Yoon, Young J; Mowry, Kimberly L (2004) Xenopus Staufen is a component of a ribonucleoprotein complex containing Vg1 RNA and kinesin. Development 131:3035-45
Kress, Tracy L; Yoon, Young J; Mowry, Kimberly L (2004) Nuclear RNP complex assembly initiates cytoplasmic RNA localization. J Cell Biol 165:203-11
Xie, Jiuyong; Lee, Ji-Ann; Kress, Tracy L et al. (2003) Protein kinase A phosphorylation modulates transport of the polypyrimidine tract-binding protein. Proc Natl Acad Sci U S A 100:8776-81
Bubunenko, Mikhail; Kress, Tracy L; Vempati, Uma Devi et al. (2002) A consensus RNA signal that directs germ layer determinants to the vegetal cortex of Xenopus oocytes. Dev Biol 248:82-92
Cote, C A; Gautreau, D; Denegre, J M et al. (1999) A Xenopus protein related to hnRNP I has a role in cytoplasmic RNA localization. Mol Cell 4:431-7
Mowry, K L; Cote, C A (1999) RNA sorting in Xenopus oocytes and embryos. FASEB J 13:435-45
Gautreau, D; Cote, C A; Mowry, K L (1997) Two copies of a subelement from the Vg1 RNA localization sequence are sufficient to direct vegetal localization in Xenopus oocytes. Development 124:5013-20

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