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 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.
Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Gabriela
G
Galicia-Vázquez
Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Sergio
S
Di Marco
Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Xian J
XJ
Lian
Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Jennifer F
JF
Ma
Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Imed E
IE
Gallouzi
Department of Biochemistry, McGill University, Montreal, Quebec, Canada ; The Rosalind and Morris Goodman Cancer Research Center, McGill University, Montreal, Quebec, Canada.
Jerry
J
Pelletier
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D039601:Eukaryotic Initiation Factor-4A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D020033:Protein Isoforms; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D039601:Eukaryotic Initiation Factor-4A