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Regulation of mRNA export by the PI3 kinase/AKT signal transduction pathway

Alexandre Jose Christino Quaresma1, Rachel Sievert, Jeffrey A Nickerson

  • 1Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA.

Molecular Biology of the Cell
|February 22, 2013
PubMed

Insights

The phosphatidylinositide 3-kinase (PI3 kinase)/AKT pathway regulates mRNA export complex assembly. Its inhibition enhances the export of poly(A) RNA and specific mRNAs, suggesting a role in nuclear mRNA retention.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • mRNA export factors UAP56, ALY/REF, and NXF1 associate with the exon junction complex (EJC).
  • Signal transduction pathways regulating mRNA export complex assembly are not fully understood.

Purpose of the Study:

  • To screen for signal transduction pathways that regulate the assembly of mRNA export complexes.
  • To investigate the role of the PI3 kinase/AKT pathway in mRNA export.

Main Methods:

  • Utilized fluorescence recovery after photobleaching (FRAP) to measure protein binding in nuclear complexes.
  • Employed drug inhibition of the PI3 kinase/AKT and mTORC1 pathways.
  • Analyzed the export of poly(A) RNA and specific candidate mRNAs.

Main Results:

  • Inhibition of the PI3 kinase/AKT pathway reduced the tight binding of UAP56, ALY/REF, NXF1, and core EJC proteins (eIF4A3, MAGOH, Y14).
  • mTORC1 inhibition decreased MAGOH binding.
  • PI3 kinase/AKT inhibition increased poly(A) RNA export and export of a subset of mRNAs, including those from histone genes, but not ER or mitochondria-targeted mRNAs.

Conclusions:

  • The active PI3 kinase/AKT pathway regulates mRNA export complex assembly.
  • This pathway promotes the nuclear retention of specific mRNAs.
  • PI3 kinase/AKT signaling is a key regulator of mRNA export dynamics.

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