The coordinate regulation of histone protein metabolism with replication of DNA is an important challenge for all organisms. While the cell cycle regulation of histone mRNA in somatic cells is relatively well understood, different mechanisms are used by the early embryo to control the storage and production of histone mRNA for the early cell cycles. Different organisms have solved this problem in distinct ways, and we explore the molecular basis of these different strategies in this proposal. Typically, histone mRNAs are not coordinately regulated with DNA replication in oogenesis and early embryogenesis, but these same mRNAs become cell-cycle regulated sometime after the rapid cleavage phase of embryogenesis. We are studying the molecular basis of this developmental regulation concentrating on two organisms, Xenopus and Drosophila. The key regulatory proteins, SLBPs, bind the 3' end of histone mRNAs. In Xenopus the two SLBPs participate in the storage and translation activation of the histone mRNAs, and using chimeric proteins we are dissecting the molecular function of different parts of each protein. There is a single SLBP in Drosophila, and we are determining how this protein participates in storage of histone mRNA and protein in the developing egg, and then how zygotic synthesis of the protein leads to the development of the normal cell-cycle regulatory pattern of histone mRNA expression. Using genetics, we will identify novel genes involved in biosynthesis and regulation of histone mRNA levels. ? ?
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