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FLASH, a proapoptotic protein involved in activation of caspase-8, is essential for 3' end processing of histone

Xiao-Cui Yang1, Brandon D Burch, Yan Yan

  • 1Department of Biochemistry and Biophysics and Program in Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Molecular Cell
|October 27, 2009
PubMed

Insights

The proapoptotic protein FLASH is essential for histone pre-mRNA 3' end maturation. It interacts with Lsm11 within the U7 snRNP complex, ensuring proper processing in both vertebrates and invertebrates.

Area of Science:

  • Molecular Biology
  • RNA Processing
  • Apoptosis

Background:

  • Histone pre-mRNA 3' end processing is crucial for gene expression and requires the U7 small nuclear ribonucleoprotein (snRNP).
  • The U7 snRNP features a unique Sm ring composition, notably replacing SmD2 with Lsm11.

Purpose of the Study:

  • To identify binding partners of Lsm11.
  • To investigate the role of identified binding partners in histone pre-mRNA 3' end processing.
  • To explore the evolutionary conservation of this interaction and its functional significance.

Main Methods:

  • Yeast two-hybrid system for identifying protein-protein interactions.
  • In vitro binding assays using recombinant proteins.
  • In vivo studies in mammalian nuclear extracts and Drosophila melanogaster.
  • Localization studies using fluorescent tagging in Drosophila cells.
  • Functional assays involving depletion of the identified protein.

Main Results:

  • The proapoptotic protein FLASH was identified as a binding partner of Lsm11.
  • Human FLASH interacts with Lsm11 in vitro and enhances histone pre-mRNA 3' end processing in mammalian extracts.
  • Drosophila FLASH interacts with Lsm11 both in vitro and in vivo.
  • Drosophila FLASH localizes to histone locus bodies and its depletion leads to aberrant polyadenylation of histone mRNAs.
  • These findings highlight FLASH as a conserved factor in U7-dependent histone pre-mRNA processing.

Conclusions:

  • FLASH is an essential protein for the 3' end maturation of histone mRNAs in both vertebrates and invertebrates.
  • The interaction between FLASH and Lsm11 is critical for U7 snRNP function.
  • This study suggests a potential mechanistic link between histone mRNA processing and the apoptotic pathway.

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