Regulation of mRNA Export by the PI3 kinase / AKT Signal Transduction Pathway
UMass Chan Affiliations
Department of Cell and Developmental BiologyDocument Type
Journal ArticlePublication Date
2013-04-15Keywords
RNA, MessengerRNA Transport
Phosphatidylinositol 3-Kinases
Signal Transduction
Cell and Developmental Biology
Enzymes and Coenzymes
Genetics and Genomics
Molecular Biology
Nucleic Acids, Nucleotides, and Nucleosides
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Show full item recordAbstract
UAP56, ALY/REF, and NXF1 are mRNA export factors that sequentially bind at the 5' end of a nuclear mRNA, but are also reported to associate with the Exon Junction Complex (EJC). To screen for signal transduction pathways regulating mRNA export complex assembly we used Fluorescence Recovery after Photobleaching (FRAP) to measure the binding of mRNA export and EJC core proteins in nuclear complexes. The fraction of UAP56, ALY/REF, and NXF1 tightly bound in complexes was reduced by drug inhibition of the PI3 kinase / AKT pathway, as was the tightly bound fraction of the core EJC proteins eIF4A3, MAGOH, and Y14. Inhibition of the mTOR mTORC1 pathway decreased the tight binding of MAGOH. Inhibition of the PI3 Kinase/AKT pathway increased the export of poly(A) RNA and of a subset of candidate mRNAs. A similar effect of PI3 kinase/AKT inhibition was observed for mRNAs from both intron-containing and intron-less Histone genes. However, the nuclear export of mRNAs coding for proteins targeted to the Endoplasmic Reticulum or to Mitochondria was not affected by the PI3 kinase/AKT pathway. These results show that the active PI3 kinase/AKT pathway can regulate mRNA export and can promote the nuclear retention of some mRNAs.Source
Mol Biol Cell. 2013 Apr;24(8):1208-21. doi: 10.1091/mbc.E12-06-0450. Link to article on publisher's site
DOI
10.1091/mbc.E12-06-0450Permanent Link to this Item
http://hdl.handle.net/20.500.14038/26438PubMed ID
23427269Related Resources
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© 2013 Quaresma et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
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http://creativecommons.org/licenses/by-nc-sa/3.0/ae974a485f413a2113503eed53cd6c53
10.1091/mbc.E12-06-0450
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Except where otherwise noted, this item's license is described as <p>© 2013 Quaresma et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).</p>