FLASH, a proapoptotic protein involved in activation of caspase-8, is essential for 3' end processing of histone pre-mRNAs.
Mol Cell
; 36(2): 267-78, 2009 Oct 23.
Article
em En
| MEDLINE
| ID: mdl-19854135
ABSTRACT
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 proapoptotic 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 from 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ligação ao Cálcio
/
Precursores de RNA
/
Histonas
/
Apoptose
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Proteínas de Drosophila
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Processamento de Terminações 3' de RNA
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Proteínas Reguladoras de Apoptose
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Caspase 8
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Cell
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos