TRANSLATIONAL CONTROL IN C. ELEGANS EMBRYOS

Harvard University, Cambridge MA

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Abstract

The 3' untranslated region (UTR) of many mRNAs contains regulatory sequences that control their translation. This is a particularly prominent means of gene regulation in early embryos and is also important in differentiated cells to control growth, differentiation, and metabolism. Despite the importance of this form of gene regulation, the mechanism(s) by which sequences at the 3' end of mRNA regulate translation are unclear. Synthesis of the PAL-1 protein in the C. elegans embryo is regulated by sequences in the pal-1 3' UTR of the mRNA and the RNA-binding protein MEX-3. MEX-3 represses pal-1 translation in oocytes and early blastomeres. At the 4-cell stage, this repression is inhibited in the posterior blastomeres and pal-1 is translated in these cells. The goal of the proposed research is to investigate how MEX-3 represses pal-1 translation, and how this repression is regulated to control the pattern of pal-1 translation. The specific aims include, identifying the specific RNA sequences and proteins required to regulate pal-1 translation and then genetically and biochemically characterizing their regulation and function. Ten proteins, including MEX-3, have been identified that are required to regulate the pattern of pal- 1 translation. Six of these proteins were identified as MEX-3 interacting proteins using the yeast 2-hybrid assay. Their functions were assigned by RNA interference analysis. Three additional regulators of pal-1 translation were identified among known patterning mutants. The long-term goals of the proposed research is to elucidate the molecular mechanism(s) of 3' UTR mediated translational control and to provide insight into how patterns in early embryos are set-up by translational control.