Regulated Pumilio-2 binding controls RINGO/Spy mRNA translation and CPEB activation
Graduate School of Biomedical Sciences; Program in Molecular Medicine
Medical Subject Headings
3' Untranslated Regions; Animals; Base Sequence; Carrier Proteins; Cell Cycle Proteins; Gene Expression Regulation, Developmental; Humans; Models, Biological; Molecular Sequence Data; Oocytes; Poly(A)-Binding Proteins; Polyadenylation; Progesterone; Protein Binding; Protein Biosynthesis; RNA, Messenger; RNA-Binding Proteins; Transcription Factors; Xenopus; Xenopus Proteins; mRNA Cleavage and Polyadenylation Factors
Life Sciences | Medicine and Health Sciences
CPEB is a sequence-specific RNA-binding protein that controls the polyadenylation-induced translation of mos and cyclin B1 mRNAs in maturing Xenopus oocytes. CPEB activity requires not only the phosphorylation of S174, but also the synthesis of a heretofore-unknown upstream effector molecule. We show that the synthesis of RINGO/Spy, an atypical activator of cyclin-dependent kinases (cdks), is necessary for CPEB-directed polyadenylation. Deletion analysis and mRNA reporter assays show that a cis element in the RINGO/Spy 3'UTR is necessary for translational repression in immature (G2-arrested) oocytes. The repression is mediated by 3'UTR Pumilio-Binding Elements (PBEs), and by its binding protein Pumilio 2 (Pum2). Pum2 also interacts with the Xenopus homolog of human Deleted for Azoospermia-like (DAZL) and the embryonic poly(A)-binding protein (ePAB). Following the induction of maturation, Pum2 dissociates not only from RINGO/Spy mRNA, but from XDAZL and ePAB as well; as a consequence, RINGO/Spy mRNA is translated. These results demonstrate that a reversible Pum2 interaction controls RINGO/Spy mRNA translation and, as a result, CPEB-mediated cytoplasmic polyadenylation.
Rights and Permissions
Citation: Genes Dev. 2006 Jan 15;20(2):199-209. Link to article on publisher's site
Genes and development
Padmanabhan, Kiran and Richter, Joel D., "Regulated Pumilio-2 binding controls RINGO/Spy mRNA translation and CPEB activation" (2006). GSBS Student Publications. 928.