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[摘要]：Y-box-binding protein 1 (YB-1) binds to mRNAs and affects translation. In this study, we focused on skeletal muscle, in which YB-1 expression is restricted to the early postnatal period, and found that YB-1 binds to acetylcholine receptor alpha-subunit (AChR alpha) mRNA. Although transcription of the AChR alpha gene is known to be regulated by myogenic transcription factors, translational control of the mRNA in response to neuromuscular transmission has not been examined. In undifferentiated C2C12 myoblasts, expression of AChR alpha remained at a low level. However, translation of the mRNA was increased by knockdown of YB-1. Continued overexpression of YB-1 prevented the cells from differentiating. In myotubes, which show clustering of AChRs, translation of the mRNA was induced within 3 h after treatment with nicotine. The effect of nicotine was inhibited by alpha-bungarotoxin, and in the presence of cycloheximide the level of AChR a was reduced, even after nicotine treatment. Sucrose gradient analysis revealed that in nicotine-treated myotubes, YB-1-containing polysomes were shifted to the heavier-sedimenting fractions, and showed an apparent decrease in the amount of YB-1 bound to AChR alpha mRNA. These results suggest that in skeletal muscle cells, neural activity reduces the molar ratio of YB-1 relative to its binding AChR alpha mRNA, leading to an increase of ribosome binding to the mRNA, and thus activating translation. Furthermore, in postnatal growing mice, as has already been shown, the level of AChR alpha mRNA declined during the early period with maturation of neuromuscular synapses, but the translation level was found to increase transiently at postnatal day 10, when the level of YB-1 was markedly reduced. It is suggested that although the level of AChR alpha mRNA is reduced, the translation can be induced by alteration of the ratio of YB-1 protein to the mRNA. (C) 2011 Published by Elsevier Inc. |
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