FLASH, a Proapoptotic Protein Involved in Activation of Caspase-8, Is Essential for 3′ End Processing of Histone Pre-mRNAs
Copyright policy )FLASH, a Proapoptotic Protein Involved in Activation of Caspase-8, Is Essential for 3′ End Processing of Histone Pre-mRNAs
3′ end processing of histone pre-mRNA requires U7 snRNP, which binds downstream of the cleavage site and recruits the endonuclease CPSF-73. U7 snRNP contains a unique Sm ring in which the canonical SmD2 protein is replaced by Lsm11. We used the yeast two-hybrid system to identify binding partners of Lsm11 and selected the pro-apoptotic protein FLASH. Human FLASH interacts with Lsm11 in vitro and stimulates 3′ end processing of histone pre-mRNA in mammalian nuclear extracts. We also identified the FLASH ortholog in Drosophila and demonstrate that it interacts with Lsm11 in vitro and in vivo. Drosophila FLASH localizes to histone locus bodies and its depletion in fly cells inhibits U7-dependent processing resulting in polyadenylation of histone mRNAs. These results demonstrate that FLASH is an essential factor required for 3′ end maturation of histone mRNAs in both vertebrates and invertebrates and suggest a potential link between this process and apoptosis.
- University of North Carolina at Chapel Hill United States
Caspase 8, Base Sequence, Calcium-Binding Proteins, Molecular Sequence Data, Apoptosis, Cell Biology, Polyadenylation, Enzyme Activation, Histones, Mice, Protein Transport, Drosophila melanogaster, Genes, Reporter, RNA Precursors, Animals, Drosophila Proteins, Humans, Nucleic Acid Conformation, RNA 3' End Processing, Apoptosis Regulatory Proteins, Molecular Biology, Protein Binding
Caspase 8, Base Sequence, Calcium-Binding Proteins, Molecular Sequence Data, Apoptosis, Cell Biology, Polyadenylation, Enzyme Activation, Histones, Mice, Protein Transport, Drosophila melanogaster, Genes, Reporter, RNA Precursors, Animals, Drosophila Proteins, Humans, Nucleic Acid Conformation, RNA 3' End Processing, Apoptosis Regulatory Proteins, Molecular Biology, Protein Binding
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