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.
Post-transcriptional regulation of maternal mRNAs is responsible for many of the developmental events that occur in the early stages of embryogenesis. By understanding the mechanisms that regulate mRNAs during embryogenesis our research will identify how this control is tied to the development of living cells and will ultimately provide insights into the molecular basis of congenital developmental diseases.
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| Massi, Francesca; Peng, Jeffrey W (2018) Characterizing Protein Dynamics with NMR R 1? Relaxation Experiments. Methods Mol Biol 1688:205-221 |
| Dowdle, Megan E; Imboden, Susanne Blaser; Park, Sookhee et al. (2017) Horizontal Gel Electrophoresis for Enhanced Detection of Protein-RNA Complexes. J Vis Exp : |
