STABILIZATION OF SLOW TROPONIN-C POLYPEPTIDE COMPENSATES FOR ITS REDUCED SYNTHESIS IN ANTISENSE OLIGODEOXYNUCLEOTIDE-TREATED CELLS

The expression of genes for contractile proteins during myogenesis is coordinately regulated. Uncoupling the expression of the slow/cardiac troponin C (sTnC) gene from this process with an antisense phosphoroth ioate oligodeoxynucleotide (ODN) was used to examine the presence of a ny post-transcriptional mechanisms for regulating muscle protein synth esis. Approximately 70 and 50% decreases in sTnC polypeptide synthesis and mRNA levels, respectively, were achieved after 4 days antisense t reatment. This decrease in sTnC polypeptide synthesis was not reflecte d in a similar decline in the steady-state level of this polypeptide, Extension of the ODN treatment to 7 days was required to produce a sub stantial decrease in the steady-state level of sTnC polypeptide. Our i nvestigation suggests that during the Q-day treatment, the affected ce lls stabilized the sTnC polypeptide level by increasing its half-life. However, the stabilizing effect appears to be overridden during prolo nged (7 days) antisense ODN treatment. Measurement of the polypeptide synthesis and mRNA levels of several contractile proteins showed no ev idence of cross-regulation among the genes to coordinately regulate th eir expression levels.