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

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 pho...

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Autores principales: Quaresma, Alexandre Jose Christino, Sievert, Rachel, Nickerson, Jeffrey A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623641/
https://www.ncbi.nlm.nih.gov/pubmed/23427269
http://dx.doi.org/10.1091/mbc.E12-06-0450
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author Quaresma, Alexandre Jose Christino
Sievert, Rachel
Nickerson, Jeffrey A.
author_facet Quaresma, Alexandre Jose Christino
Sievert, Rachel
Nickerson, Jeffrey A.
author_sort Quaresma, Alexandre Jose Christino
collection PubMed
description 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 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 phosphatidylinositide 3-kinase (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 intronless 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 promote the nuclear retention of some mRNAs.
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spelling pubmed-36236412013-06-30 Regulation of mRNA export by the PI3 kinase/AKT signal transduction pathway Quaresma, Alexandre Jose Christino Sievert, Rachel Nickerson, Jeffrey A. Mol Biol Cell Articles 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 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 phosphatidylinositide 3-kinase (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 intronless 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 promote the nuclear retention of some mRNAs. The American Society for Cell Biology 2013-04-15 /pmc/articles/PMC3623641/ /pubmed/23427269 http://dx.doi.org/10.1091/mbc.E12-06-0450 Text en © 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). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Quaresma, Alexandre Jose Christino
Sievert, Rachel
Nickerson, Jeffrey A.
Regulation of mRNA export by the PI3 kinase/AKT signal transduction pathway
title Regulation of mRNA export by the PI3 kinase/AKT signal transduction pathway
title_full Regulation of mRNA export by the PI3 kinase/AKT signal transduction pathway
title_fullStr Regulation of mRNA export by the PI3 kinase/AKT signal transduction pathway
title_full_unstemmed Regulation of mRNA export by the PI3 kinase/AKT signal transduction pathway
title_short Regulation of mRNA export by the PI3 kinase/AKT signal transduction pathway
title_sort regulation of mrna export by the pi3 kinase/akt signal transduction pathway
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623641/
https://www.ncbi.nlm.nih.gov/pubmed/23427269
http://dx.doi.org/10.1091/mbc.E12-06-0450
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