CAP RIBOSE METHYLATION OF C-MOS MESSENGER-RNA STIMULATES TRANSLATION AND OOCYTE MATURATION IN XENOPUS-LAEVIS

In Xenopus oocytes, progesterone stimulates the cytoplasmic polyadenyl ation and resulting translational activation of c-mos mRNA, which is n ecessary for the induction of oocyte maturation, Although details of t he biochemistry of polyadenylation are beginning to emerge, the mechan ism by which 3' poly(A) addition stimulates translation initiation is enigmatic. A previous report showed that polyadenylation induced cap-s pecific 2'-O-methylation, and suggested that this 5' end modification was important for translational activation. Here, we demonstrate that injected c-mos RNA undergoes polyadenylation and cap ribose methylatio n. Inhibition of this methylation by S-isobutylthio-adenosine (SIBA), a methyltransferase inhibitor, has little effect on progesterone-induc ed c-mos mRNA polyadenylation or general protein synthesis, but preven ts the synthesis of Mos protein as well as oocyte maturation. Maturati on can be rescued, however, by the injection of factors that act downs tream of Mos, such as cyclin A and B mRNAs, Most importantly, we show that the translational efficiency of injected mRNAs containing cap-spe cific 2'-O-methylation (cap I) is significantly enhanced compared to R NAs that do not contain the methylated ribose (cap 0), These results s uggest that cap ribose methylation of c-mos mRNA is important for tran slational recruitment and for the progression of oocytes through meios is.