A Molecular and Genetic Characterization of the Mechanisms of Histone mRNA Metabolism in Drosophila Public Deposited

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  • March 19, 2019
  • Kupsco, Jeremy Matthew
    • Affiliation: College of Arts and Sciences, Department of Biology
  • In metazoans the replication dependent histones are produced during S-phase of the cell cycle. The timely production of histones during S-phase is required to quickly package the newly synthesized DNA. Much of this S-phase regulation is achieved by the regulation of histone pre-mRNA processing. Histone mRNAs are the only mRNAs in metazoans that do not end in a poly(A) tail instead ending in a conserved 26 nucleotide sequence that forms a stem loop. A protein called Stem Loop Binding Protein (SLBP) binds to the stem loop which along with the U7 snRNP recruits an endonuclease complex to cleave the histone pre-mRNA to create the mature histone transcript. Drosophila contains a single SLBP gene, which is required for histone pre-mRNA processing during embryogenesis, the larval stages of development, and during oogenesis. In the absence of SLBP, histone mRNAs become polyadenylated by the use of cryptic polyadenylation sites downstream of the normal cleavage site. These polyadenylated transcripts perdure outside of S-phase in cells that are undergoing endocycles. In addition to Drosophila SLBP's role in histone pre-mRNA processing, a 53 amino acid region of the N-terminus is required for viability of the organism but is dispensable for histone mRNA processing indicating a second function for SLBP in histone metabolism. At the end of S-phase histone mRNAs are rapidly destroyed. The human protein 3'hExo has been implicated in the degradation of histone mRNAs. Drosophila contains a single potential homologue of 3'hExo, Snipper, which is capable of degrading and binding to histone mRNAs in vitro. However, in Snipper mutant flies no defect in histone mRNA degradation was seen, indicating that Snipper is not required for the regulated destruction of histone mRNAs and has a yet to be discovered function.
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  • Duronio, Robert
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