The polyadenylation inhibitor cordycepin (3'dA) causes a decline in c-MYC mRNA levels without affecting c-MYC protein levels.

Abstract

Study of the distribution of the poly(A) tail length of c-myc mRNA in several cell lines revealed a distinct, prevailing population with short poly(A) tails, derived through sequential deadenylation. To elucidate the possible in vivo function of this distinct short tailed c-myc mRNA population, the polyadenylation inhibitor cordycepin was used. This resulted in a decline in steady state c-myc mRNA levels with the remaining messenger mostly oligoadenylated. However, c-MYC proteins did not follow the reduction of the c-myc mRNA. On the other hand, in cells exposed to physiological agents known to downregulate c-myc expression, the reduction of mRNA steady state levels, was reflected upon c-MYC protein levels. The dissociation between c-myc mRNA and protein levels caused by cordycepin was not due to the stabilization of the c-MYC proteins and was not an indiscriminate effect since in the presence of cordycepin, c-fos mRNA and protein levels concomitantly declined. Our data indicate that under these conditions, a long poly(A) tail is not instrumental for c-myc mRNA translation and furthermore, the discrepancy in the steady state of c-myc mRNA level: c-MYC protein ratio between control cells and cells treated with cordycepin indicates that c-myc mRNA is subjected to translational control.