Histone mRNAs are tightly regulated during the mammalian cell cycle. Most of the regulation is post-transcriptional, mediated by the 3' end of histone mRNA. The protein that binds to the 3 end of histone mRNA, the stem-loop binding protein SLBP, is a likely candidate to mediate the post-transcriptional regulation of histone mRNA. The levels of SLBP are also tightly regulated during the mammalian cell cycle. The signals regulating histone mRNA metabolism are likely to be important in the regulation of cell growth, and hence be possible targets for novel chemotherapy approaches. The mechanisms by which histone mRNA expression is coupled to the known regulators of the cell cycle are not understood. This proposal will elucidate the molecular mechanisms by which SLBP is regulated, focusing on regions in the protein, which regulate the half-life of histone mRNA and on the sequences in SLBP mRNA, which regulate its translation.
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