Molecular mechanisms underlying the activity-linked alterations in acetylcholinesterase mRNAs in developing versus adult rat skeletal muscles

The molecular mechanisms underlying the activity-linked plasticity of acety lcholinesterase (AChE) mRNA levels in mammalian skeletal muscle have yet to be established. Here, we demonstrate that denervation of adult muscle indu ces a dramatic (up to 90%) and rapid (within 24 h) decrease in the abundanc e of AChE mRNAs. By contrast, denervation of 14-day-old rats leads to a sig nificantly less pronounced reduction (50% of control) in the expression of AChE mRNAs. Assessment of the transcriptional activity of the AChE gene rev eals that it remains essentially unchanged in adult denervated muscles, whe reas it displays an approximately two- to threefold increase (p < 0.05) in denervated muscles from 2- to 14-day-old rats. In addition, we observed a h igher rate of degradation of in vitro transcribed AChE mRNAs upon incubatio n with protein extracts from denervated muscles. Finally, UV-crosslinking e xperiments reveal that denervation increases the abundance of RNA-protein i nteractions in the 3' untranslated region of AChE transcripts. Taken togeth er, these data suggest that the abundance of AChE transcripts in mature mus cles is controlled primarily via posttranscriptional regulatory mechanisms, whereas in neo- and postnatal muscles, both transcriptional and posttransc riptional regulation appears critical in dictating AChE mRNA levels. Accord ingly, the activity-linked transcriptional regulation of the AChE gene appe ars to demonstrate a high level of plasticity during muscle development whe n maturation of the neuromuscular junctions is still occurring.