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A Reporter Assay to Analyze Intronic microRNA Maturation in Mammalian Cells
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A Reporter Assay to Analyze Intronic microRNA Maturation in Mammalian Cells

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Signaling by p38 MAPK stimulates nuclear localization of the microprocessor component p68 for processing of selected

Sungguan Hong1, Hyangsoon Noh, Haoming Chen

  • 1Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Health Sciences University, Augusta, GA 30912, USA. shuang@gru.edu

Science Signaling
|March 14, 2013
PubMed

Insights

The p38 MAPK-MK2 pathway is crucial for microRNA (miRNA) production. This pathway ensures the nuclear localization of p68, a key protein in miRNA processing, thereby promoting miRNA biogenesis.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Gene Regulation

Background:

  • MicroRNAs (miRNAs) regulate gene expression and are vital in biological and disease processes.
  • Understanding miRNA biogenesis mechanisms is essential for therapeutic development.
  • The mitogen-activated protein kinase (MAPK) p38 pathway plays a role in cellular regulation.

Purpose of the Study:

  • To investigate the role of the p38 MAPK-MK2 signaling pathway in miRNA biogenesis.
  • To identify the specific molecular mechanisms by which this pathway influences miRNA processing.
  • To explore the implications of this pathway in cell growth and cancer.

Main Methods:

  • Yeast two-hybrid screening to identify protein interactions.
  • In vitro kinase assays and Western blotting to detect protein phosphorylation.
  • Analysis of primary miRNA (pri-miRNA) processing in wild-type and knockout mouse embryonic fibroblasts (MEFs).
  • Cellular localization studies using microscopy.

Main Results:

  • The MAPK p38 and its effector kinase MK2 are necessary for efficient processing of a subset of pri-miRNAs.
  • MK2 directly phosphorylates p68 (DDX5) at Ser(197), which is essential for pri-miRNA processing.
  • MK2-mediated phosphorylation of p68 is required for its nuclear localization.
  • Inhibition of p38 MAPK promotes cell growth by downregulating miR-145, leading to increased c-Myc levels.

Conclusions:

  • The p38 MAPK-MK2 signaling pathway promotes miRNA biogenesis by facilitating the nuclear localization of p68.
  • This pathway represents a potential therapeutic target for diseases involving aberrant miRNA expression.
  • The findings provide new insights into the regulation of miRNA processing and its role in cell proliferation.

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