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The AU-rich element mRNA decay-promoting activity of BRF1 is regulated by mitogen-activated protein kinase-activated

Sushmit Maitra1, Chu-Fang Chou, Christian A Luber

  • 1Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

RNA (New York, N.Y.)
|March 8, 2008
PubMed

Insights

MAPK-activated protein kinase 2 (MK2) directly phosphorylates BRF1, inhibiting its role in AU-rich element-mediated mRNA decay (AMD). This phosphorylation event regulates gene expression by controlling mRNA stability.

Area of Science:

  • Molecular Biology
  • Gene Expression Regulation
  • RNA Metabolism

Background:

  • Regulated mRNA decay is crucial for controlling gene expression.
  • AU-rich elements (AREs) in 3' untranslated regions target mRNAs for rapid decay via ARE-binding proteins (ARE-BPs).
  • Signaling pathways are known to regulate ARE-containing mRNA decay, likely by targeting ARE-BPs.

Purpose of the Study:

  • To investigate the role of MAPK-activated protein kinase 2 (MK2) in AU-rich element-mediated mRNA decay (AMD).
  • To determine if MK2 directly interacts with and modifies BRF1, a key protein in AMD.
  • To elucidate the mechanism by which MK2 influences BRF1 activity and subsequent mRNA decay.

Main Methods:

  • In vitro kinase assays using BRF1 fragments to identify phosphorylation sites.
  • Coexpression studies to assess the effect of active MK2 on BRF1's mRNA decay activity.
  • Analysis of BRF1's interaction with AREs and mRNA decay enzymes following MK2 phosphorylation.

Main Results:

  • MK2 directly phosphorylates BRF1 at four distinct sites, including S54, S92, and S203.
  • Active MK2 significantly inhibits BRF1's ARE-mediated mRNA decay activity.
  • MK2-mediated inhibition of BRF1 is dependent on phosphorylation at S54, S92, and S203, and does not affect RNA binding or association with decay enzymes.

Conclusions:

  • MK2 directly phosphorylates BRF1, leading to the inhibition of BRF1-dependent AMD.
  • The inhibitory mechanism appears to act downstream of RNA binding and enzyme recruitment.
  • MK2 represents a key regulatory point in controlling gene expression through modulation of mRNA stability.

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