Regulation of eukaryotic initiation factor 4AII by MyoD during murine myogenic cell differentiation.

Gene expression during muscle cell differentiation is tightly regulated at multiple levels, including translation initiation. The PI3K/mTOR signalling pathway exerts control over protein synthesis by regulating assembly of eukaryotic initiation factor (eIF) 4F, a heterotrimeric complex that stimulat...

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Main Authors: Gabriela Galicia-Vázquez, Sergio Di Marco, Xian J Lian, Jennifer F Ma, Imed E Gallouzi, Jerry Pelletier
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3900710?pdf=render
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author Gabriela Galicia-Vázquez
Sergio Di Marco
Xian J Lian
Jennifer F Ma
Imed E Gallouzi
Jerry Pelletier
author_facet Gabriela Galicia-Vázquez
Sergio Di Marco
Xian J Lian
Jennifer F Ma
Imed E Gallouzi
Jerry Pelletier
author_sort Gabriela Galicia-Vázquez
collection DOAJ
description Gene expression during muscle cell differentiation is tightly regulated at multiple levels, including translation initiation. The PI3K/mTOR signalling pathway exerts control over protein synthesis by regulating assembly of eukaryotic initiation factor (eIF) 4F, a heterotrimeric complex that stimulates recruitment of ribosomes to mRNA templates. One of the subunits of eIF4F, eIF4A, supplies essential helicase function during this phase of translation. The presence of two cellular eIF4A isoforms, eIF4AI and eIF4AII, has long thought to impart equivalent functions to eIF4F. However, recent experiments have alluded to distinct activities between them. Herein, we characterize distinct regulatory mechanisms between the eIF4A isoforms during muscle cell differentiation. We find that eIF4AI levels decrease during differentiation whereas eIF4AII levels increase during myofiber formation in a MyoD-dependent manner. This study characterizes a previously undefined mechanism for eIF4AII regulation in differentiation and highlights functional differences between eIF4AI and eIF4AII. Finally, RNAi-mediated alterations in eIF4AI and eIF4AII levels indicate that the myogenic process can tolerate short term reductions in eIF4AI or eIF4AII levels, but not both.
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spelling doaj.art-0df4c202c8244fadac522a12b61024a82022-12-22T01:56:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0191e8723710.1371/journal.pone.0087237Regulation of eukaryotic initiation factor 4AII by MyoD during murine myogenic cell differentiation.Gabriela Galicia-VázquezSergio Di MarcoXian J LianJennifer F MaImed E GallouziJerry PelletierGene expression during muscle cell differentiation is tightly regulated at multiple levels, including translation initiation. The PI3K/mTOR signalling pathway exerts control over protein synthesis by regulating assembly of eukaryotic initiation factor (eIF) 4F, a heterotrimeric complex that stimulates recruitment of ribosomes to mRNA templates. One of the subunits of eIF4F, eIF4A, supplies essential helicase function during this phase of translation. The presence of two cellular eIF4A isoforms, eIF4AI and eIF4AII, has long thought to impart equivalent functions to eIF4F. However, recent experiments have alluded to distinct activities between them. Herein, we characterize distinct regulatory mechanisms between the eIF4A isoforms during muscle cell differentiation. We find that eIF4AI levels decrease during differentiation whereas eIF4AII levels increase during myofiber formation in a MyoD-dependent manner. This study characterizes a previously undefined mechanism for eIF4AII regulation in differentiation and highlights functional differences between eIF4AI and eIF4AII. Finally, RNAi-mediated alterations in eIF4AI and eIF4AII levels indicate that the myogenic process can tolerate short term reductions in eIF4AI or eIF4AII levels, but not both.http://europepmc.org/articles/PMC3900710?pdf=render
spellingShingle Gabriela Galicia-Vázquez
Sergio Di Marco
Xian J Lian
Jennifer F Ma
Imed E Gallouzi
Jerry Pelletier
Regulation of eukaryotic initiation factor 4AII by MyoD during murine myogenic cell differentiation.
PLoS ONE
title Regulation of eukaryotic initiation factor 4AII by MyoD during murine myogenic cell differentiation.
title_full Regulation of eukaryotic initiation factor 4AII by MyoD during murine myogenic cell differentiation.
title_fullStr Regulation of eukaryotic initiation factor 4AII by MyoD during murine myogenic cell differentiation.
title_full_unstemmed Regulation of eukaryotic initiation factor 4AII by MyoD during murine myogenic cell differentiation.
title_short Regulation of eukaryotic initiation factor 4AII by MyoD during murine myogenic cell differentiation.
title_sort regulation of eukaryotic initiation factor 4aii by myod during murine myogenic cell differentiation
url http://europepmc.org/articles/PMC3900710?pdf=render
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