Structural basis for post-transcriptional regulation in C. elegans

Univ Of Massachusetts Med Sch Worcester, Worcester MA

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Abstract

During metazoan development, polarization of the body axes is of critical importance, as asymmetric cell division initiates cell specialization pathways. A family of conserved RNA-binding proteins characterized by CCCH-type tandem zinc finger (TZF) domains is required for axis polarization and cell type specification in the early embryo of C. elegans. A cascade of events essential to the oocyte- to-embryo transition is driven by three members of this family. The process initiates with OMA-1/2 turnover and culminates with asymmetric segregation of POS-1 and MEX-5/6 to opposing poles of the embryo. Mutation of OMA-1/2 blocks oocyte maturation and prevents fertilization. Mutation of MEX-5/6 or POS-1 leads to embryonic death with abnormal cell fate specification. Although these TZF domains are characterized by high sequence homology, they have evolved to have different propensities toward intrinsic disorder and recognize diverse RNA sequences. Our goal is to define the molecular basis of RNA recognition and binding specificity using NMR spectroscopy, computer simulations, and quantitative biochemistry. We will probe how different structural plasticity and RNA-binding activity contribute to each protein's biological activity in worms. This research will lead to a new understanding of the factors that determine RNA affinity and specificity and their role in embryogenesis.