During the early development of many animal species, the expression of new genetic information is governed by selective translation of stored maternal mRNAs. In many cases, this translational activation requires cytoplasmic poly(A) elongation. However, how this modification at the 3′ end of an mRNA stimulates translation from the 5′ end is unknown. Here we show that cytoplasmic polyadenylation stimulates cap ribose methylation during progesterone‐induced oocyte maturation in Xenopus laevis. Translational recruitment of a chimeric reporter mRNA that is controlled by cytoplasmic polyadenylation coincides temporally with cap ribose methylation during this period. In addition, the inhibition of cap ribose methylation by S‐isobutyladenosine significantly reduces translational activation of a reporter mRNA without affecting the increase of general protein synthesis or polyadenylation during maturation. These results provide evidence for a functional interaction between the termini of an mRNA molecule and suggest that 2′‐O‐ribose cap methylation mediates the translational recruitment of maternal mRNA.

In Xenopus oocytes, progesterone stimulates the cytoplasmic polyadenylation and resulting translational activation of c-mos mRNA, which is necessary for the induction of oocyte maturation. Although details of the biochemistry of polyadenylation are beginning to emerge, the mechanism by which 3' poly(A) addition stimulates translation initiation is enigmatic. A previous report showed that polyadenylation induced cap-specific 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 methylation. Inhibition of this methylation by S-isobutylthioadenosine (SIBA), a methyltransferase inhibitor, has little effect on progesterone-induced c-mos mRNA polyadenylation or general protein synthesis, but prevents the synthesis of Mos protein as well as oocyte maturation. Maturation can be rescued, however, by the injection of factors that act downstream of Mos, such as cyclin A and B mRNAs. Most importantly, we show that the translational efficiency of injected mRNAs containing cap-specific 2'-O-methylation (cap I) is significantly enhanced compared to RNAs that do not contain the methylated ribose (cap 0). These results suggest that cap ribose methylation of c-mos mRNA is important for translational recruitment and for the progression of oocytes through meiosis.

Background:In neurons, the plasma membrane is separated into functional segments. Results: A phospholipid with a unique acyl chain composition is concentrated at the tips of neuronal projections, which is necessary for the confinement of proteins at the site. Conclusion:The neuronal plasma membrane is compartmentalized by a unique phospholipid species. Significance: This reveals a novel mode of membrane compartmentalization.

No abstract

Objectives: To clarify the underlying molecular mechanism of corticosterone methyl oxidase type II (CMO II) deficiency, Japanese patients newly diagnosed with CMO II deficiency were investigated. Methods: We analyzed the patients’ genomic DNA sequence on all 9 exons of the CYP11B2 gene. In addition, restriction fragment length polymorphism (RFLP) analysis and expression studies were performed. Results: The analysis showed that the patients homozygously retained a missense mutation, GGC[⁴³⁵Gly]→AGC[Ser], in the CYP11B2 gene. Expression studies indicated that the steroid 18-hydroxylase/oxidase activities of the mutant enzyme were substantially reduced. Conclusion: These results support the hypothesis that this mutation causes CMO II deficiency in the patients, and are in accordance with our theory that the partial loss of P-450_C18 activities causes CMO II deficiency.