This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The goal of this research is to add to our understanding of the eukaryotic cell cycle. In particular, this work will investigate how this very complicated biological process is regulated. Thorough knowledge of the mechanisms controlling the cell cycle is necessary for building an understanding of how cell division control is lost in cancer cells. An important model system for studying the cell cycle is oocyte development in the frog, Xenopus laevis. The proposed research investigates how translational regulation of oocyte mRNAs is achieved. In oocytes, maternal mRNAs code for proteins critical to cell cycle regulation. One protein that regulates oocyte mRNA translation has been characterized, but substantial evidence indicates that the Wee1 mRNA is bound by a novel protein at a site termed the translational control sequence (TCS), and that this binding is important for translational control. The Wee1 mRNA encodes a protein that is one of the key regulatory elements of cell cycle control, in particular of events early in the process of cell division. The proposed research includes the following specific aims that will enhance our knowledge of protein:RNA interactions in translational regulation: (1) The TCS-binding protein (TCSB) will be obtained through the yeast three-hybrid screening protocol (2) The expression of TCSB RNA and protein will be characterized, and details about the protein?s involvement in Wee1 translation will be acquired. (3) Other proteins that interact with TCSB and help make translational control possible will be identified and analyzed. (4) Additional RNAs that are regulated by TCSB binding will be discovered. Successful completion of these goals will lead to a more in-depth perception of cell cycle control in Xenopus, and also in other organisms including humans.
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