RINGO/cdk1 and CPEB mediate poly(A) tail stabilization and translational regulation by ePAB

• Published in: Genes & development 2007-10, Vol.21 (20), p.2571-2579
• Main Authors: Kim, Jong Heon, Richter, Joel D
• Format: Article
• Language: English
• Subjects: Amino Acid Substitution; Animals; CDC2 Protein Kinase - genetics; CDC2 Protein Kinase - metabolism; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Eukaryotic Initiation Factor-4G - genetics; Eukaryotic Initiation Factor-4G - metabolism; Female; In Vitro Techniques; Models, Biological; mRNA Cleavage and Polyadenylation Factors - chemistry; mRNA Cleavage and Polyadenylation Factors - genetics; mRNA Cleavage and Polyadenylation Factors - metabolism; Mutagenesis, Site-Directed; Oocytes - metabolism; Poly(A)-Binding Proteins - genetics; Poly(A)-Binding Proteins - metabolism; Protein Biosynthesis; Research Paper; RNA Stability; RNA, Messenger - genetics; RNA, Messenger - metabolism; Transcription Factors - chemistry; Transcription Factors - genetics; Transcription Factors - metabolism; Xenopus laevis; Xenopus Proteins - chemistry; Xenopus Proteins - genetics; Xenopus Proteins - metabolism
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.1593007

One activity that controls mRNA translation in vertebrate oocytes, embryos, and neurons is cytoplasmic polyadenylation. In Xenopus oocytes, where much of the biochemistry of this process has been elucidated, nuclear pre-mRNAs containing a cytoplasmic polyadenylation element (CPE) in their 3' untranslated regions (UTRs) have long poly(A) tails; once the RNAs are spliced and transported to the cytoplasm, the tails are shortened. Following the resumption of meiosis, the poly(A) tails are lengthened and translation ensues. CPEB is a sequence-specific RNA-binding protein that coordinates these events and does so by binding to the CPE as well as several factors including Gld2, a poly(A) polymerase, and PARN [poly(A)-specific ribonuclease], a deadenylase. Here, we show that ePAB, embryonic poly(A)-binding protein, transiently associates with the polyadenylation complex; it initially interacts with CPEB, but after polyadenylation, it binds the poly(A) tail. ePAB dissociation from CPEB is regulated by RINGO (Rapid Inducer of G(2)/M progression in Oocytes), a cyclin B1-like cofactor that activates cdk1, a protein kinase that phosphorylates CPEB. Subsequent ePAB binding to the poly(A) tail is necessary to protect the homopolymer from degradation by deadenylating enzymes. Poly(A)-bound ePAB also interacts with eIF4G, which instigates translation initiation of CPEB-bound mRNAs.