The control of mRNA/protein complexes (mRNPs) is critical to animal development and cell function. Little is known about how specific mRNPs are regulated, and how this control is organized in the cytoplasm of living cells. This project plans to use C. elegans germ line and embryonic development to address this problem. In C. elegans, the translation of Notch/glp-1 and other mRNAs is tightly regulated to produce precisely localized proteins that control early development. For Notch/glp-1 several regulators including the KH protein GLD-1 and PDF proteins function at distinct stages and through distinct 3'UTR elements to mediate this control. Some of these regulators have been found in large mRNP complexes with conserved general mRNA factors. For this project, a combination of in situ detection and biochemical isolation methods will be used to determine the composition of glp-1 and other mRNPs during oocyte and embryonic development. Injection of tagged RNAs will be done to determine how RNA elements and protein factors control mRNP assembly and translation in vivo. Mutants and RNAi will be used to determine the functions of known and novel genes in these events. These studies will reveal new insights into the mechanisms that control developmentally critical mRNPs and how those mechanisms are linked to cell determination and organization. Notch and its regulators in C. elegans are conserved in humans, and defects in them are linked to cancer and neurological abnormalities. Thus, these studies may illuminate disease mechanisms, and could lead to novel strategies to control these genes in people. Relevance to public health: This study will uncover processes that control cell development, growth, and regulation in people. Defects in these processes lead to cancer, neurological disorders, and a variety of additional diseases. This work will lead to novel strategies to control genes and fix defects that lead to these diseases.

R01GM079682

2007-08-01

2012-05-31