Journal Article

Translational control by CPEB: a means to the end

Richter, Joel D., Mendez, Raul

2001

Overview

Key Points The regulated translation of messenger RNAs is crucial for many developmental processes, including oocyte maturation, establishment of the embryonic axes, and regulation of 'synaptic memory' in the central nervous system. The initiation complex is a key target for both positive and negative regulators of translation. Particular features of an mRNA also affect its translational efficiency, including sequences that lie in its 3′ and 5′ untranslated regions (UTRs). During oocyte maturation, there is an intricate network of translational activation and repression of stored maternal mRNAs. One crucial factor for this is the serine/threonine kinase Mos, one of whose functions is to induce translational activation of cyclin B1 mRNA. Intriguingly, the translation of Mos itself must first be activated during maturation. Many dormant mRNAs, including Mos and cyclin B1, contain short poly(A) tails, which must be elongated for translational initiation to occur. Polyadenylation requires two elements in the 3′ UTR: the hexanucleotide AAUAAA and the cytoplasmic polyadenylation element (CPE), the latter of which varies in copy number and distance from the hexanucleotide. The CPE is bound by CPEB, which, through an interaction with the AAUAAA-binding factor (CPSF), recruits poly(A) polymerase to the mRNA, and thus triggers polyadenylation. CPEB is also proposed to act indirectly as a masking factor, but the main protein that mediates translational repression is maskin, an eIF4E-associated factor. An attractive model is that polyadenylation relieves repression by triggering dissociation of maskin from the eIF4E, the cap binding protein. After oocyte maturation, most CPEB is destroyed, apart from that associating with spindles and centrosomes. Maskin also localizes to those structures, and both proteins are proposed to regulate translation initiation during embryonic cell divisions. One crucial target is thought to be cyclin B1 mRNA. A possible role for CPEB-mediated translational activation in neuronal synapses is indicated by the localization of CPEB in postsynaptic densities of hippocampal neurons. At this locale, synaptic plasticity may be controlled, as least in part, by the polyadenylation and translation of CPE-containing mRNAs. The regulated translation of messenger RNA is essential for cell-cycle progression, establishment of the body plan during early development, and modulation of key activities in the central nervous system. Cytoplasmic polyadenylation, which is one mechanism of controlling translation, is driven by CPEB — a highly conserved, sequence-specific RNA-binding protein that binds to the cytoplasmic polyadenylation element, and modulates translational repression and mRNA localization. What are the features and functions of this multifaceted protein?

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 3' Untranslated regions / 5' Untranslated regions / AAUAAA-binding factor / Amino acid sequence / Animals / Biochemistry / Biomedical and Life Sciences / Cancer Research / Cell Biology / Cell Cycle - physiology / Cell division / Central nervous system / Centrosomes / Conserved sequence / Copy number / CPEB protein / CPSF protein / Cyclin B1 / Cytoplasm - metabolism / Developmental Biology / Embryos / Gametocytes / Gene Expression Regulation / Hippocampus / Humans / Initiation complex / Initiation factor eIF-4E / Kinases / Life Sciences / Localization / maskin / Maturation / Models, Biological / Molecular Structure / Mos protein / mRNA / mRNA Cleavage and Polyadenylation Factors / Nervous system / Neuronal Plasticity / Nucleotide sequence / Oocytes - physiology / Phylogeny / Polyadenine / Polyadenylation / Polynucleotide adenylyltransferase / Protein Biosynthesis / Protein-serine/threonine kinase / Proteins / review-article / RNA, Messenger - metabolism / RNA-binding protein / RNA-Binding Proteins - chemistry / RNA-Binding Proteins - genetics / RNA-Binding Proteins - metabolism / Spindles / Stem Cells / Synapses / Synaptic plasticity / Transcription Factors - chemistry / Transcription Factors - genetics / Transcription Factors - metabolism / Translation initiation / Xenopus laevis - embryology / Xenopus Proteins