UMMS Affiliation

Department of Molecular Genetics and Microbiology; Program in Molecular Medicine

Date

8-30-2001

Document Type

Article

Subjects

Amino Acid Sequence; Animals; Catalysis; Cell Cycle Proteins; Cytoplasm; Meiosis; Mice; Molecular Sequence Data; Oocytes; Phosphorylation; Poly A; Protein Kinases; Protein-Serine-Threonine Kinases; RNA-Binding Proteins; Transcription Factors; *Xenopus Proteins; *Zinc Fingers; *mRNA Cleavage and Polyadenylation Factors

Disciplines

Genetics and Genomics | Microbiology

Abstract

In both vertebrates and invertebrates, the expression of several maternal mRNAs is regulated by cytoplasmic polyadenylation. In Xenopus oocytes, where most of the biochemical details of this process have been examined, polyadenylation is controlled by CPEB, a sequence-specific RNA binding protein. The activity of CPEB, which is to recruit cleavage and polyadenylation specificity factor (CPSF) and poly(A) polymerase (PAP) into an active cytoplasmic polyadenylation complex, is controlled by Eg2-catalyzed phosphorylation. Soon after CPEB phosphorylation and resulting polyadenylation take place, the interaction between maskin, a CPEB-associated factor, and eIF4E, the cap-binding protein, is destroyed, which results in the recruitment of mRNA into polysomes. Polyadenylation also occurs in maturing mouse oocytes, although the biochemical events that govern the reaction in these cells are not known. In this study, we have examined the phosphorylation of CPEB and have assessed the necessity of this protein for polyadenylation in maturing mouse oocytes. Immunohistochemistry has revealed that all the factors that control polyadenylation and translation in Xenopus oocytes (CPEB, CPSF, PAP, maskin, and IAK1, the murine homologue of Eg2) are also present in the cytoplasm of mouse oocytes. After the induction of maturation, a kinase is activated that phosphorylates CPEB on a critical regulatory residue, an event that is essential for CPEB activity. A peptide that competitively inhibits the activity of IAK1/Eg2 blocks the progression of meiosis in injected oocytes. Finally, a CPEB protein that acts as a dominant negative mutation because it cannot be phosphorylated by IAK1/Eg2, prevents cytoplasmic polyadenylation. These data indicate that cytoplasmic polyadenylation in mouse oocytes is mediated by IAK1/Eg2-catalyzed phosphorylation of CPEB.

Rights and Permissions

Citation: Development. 2001 Jul;128(14):2815-22.

Related Resources

Link to Article in PubMed

Journal Title

Development (Cambridge, England)

PubMed ID

11526086

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