Opposing polymerase-deadenylase activities regulate cytoplasmic polyadenylation.
Cytoplasmic polyadenylation is one mechanism that regulates translation in early animal development. In Xenopus oocytes, polyadenylation of dormant mRNAs, including cyclin B1, is controlled by the cis-acting cytoplasmic polyadenylation element (CPE) and hexanucleotide AAUAAA through associations with CPEB and CPSF, respectively. Previously, we demonstrated that the scaffold protein symplekin contacts CPEB and CPSF and helps them interact with Gld2, a poly(A) polymerase. Here, we report the mechanism by which poly(A) tail length is regulated. Cyclin B1 pre-mRNA acquires a long poly(A) tail in the nucleus that is subsequently shortened in the cytoplasm. The shortening is controlled by CPEB and PARN, a poly(A)-specific ribonuclease. Gld2 and PARN both reside in the CPEB-containing complex. However, because PARN is more active than Gld2, the poly(A) tail is short. When oocytes mature, CPEB phosphorylation causes PARN to be expelled from the ribonucleoprotein complex, which allows Gld2 to elongate poly(A) by default.
Kim
Jong Heon
JH
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Richter
Joel D
JD
D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D003593:Cytoplasm / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D010766:Phosphorylation; D011061:Poly A / Q000378:metabolism; D026723:Polyadenylation; D011062:Polynucleotide Adenylyltransferase / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism*; D014981:Xenopus; D014982:Xenopus laevis / Q000378:metabolism
D019926:Cyclin B; D056744:Cyclin B1; D011061:Poly A; D011062:Polynucleotide Adenylyltransferase; D004259:DNA-Directed DNA Polymerase; D012260:Ribonucleases