CPEB: a life in translation
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.Trends in Biochemical Sciences (Impact Factor: 11.23). 07/2007; 32(6):279-85. DOI: 10.1016/j.tibs.2007.04.004
Nearly two decades ago, Xenopus oocytes were found to contain mRNAs harboring a small sequence in their 3' untranslated regions that control cytoplasmic polyadenylation and translational activation during development. This cytoplasmic polyadenylation element (CPE) is the binding platform for CPE-binding protein (CPEB), which promotes polyadenylation-induced translation. Since then, the biochemistry and biology of CPEB has grown rather substantially: mechanistically, CPEB nucleates a complex of factors that regulates poly(A) elongation through, of all things, a deadenylating enzyme; biologically, CPEB mediates many processes including germ-cell development, cell division and cellular senescence, and synaptic plasticity and learning and memory. These observations underscore the growing complexities of CPEB involvement in cell function.
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- "In vertebrate oocytes, the most studied cis-acting 3′UTR element is the cytoplasmic polyadenylation element (CPE) and its binding protein (CPEB) (Mendez and Richter 2001). CPEs and CPEBs play a major role in the meiotic maturation that is driven by cytoplasmic polyadenylation and sequential translational activation of dormant maternal mRNAs (Mendez et al. 2002; Richter 2007; Piqué et al. 2008; Villalba et al. 2011; Komrskova et al. 2014). CPEB is one of many RNA binding proteins which recognize either sequence motifs or secondary structures within 3'UTRs and regulate mRNA metabolism. "
ABSTRACT: A hallmark of oocyte development in mammals is the dependence on the translation and utilization of stored RNA and proteins rather than the de novo transcription of genes in order to sustain meiotic progression and early embryo development. In the absence of transcription, the completion of meiosis and early embryo development in mammals relies significantly on maternally synthesized RNAs. Post-transcriptional control of gene expression at the translational level has emerged as an important cellular function in normal development. Therefore, the regulation of gene expression in oocytes is controlled almost exclusively at the level of mRNA and protein stabilization and protein synthesis. This current review is focused on the recently emerged findings on RNA distribution related to the temporal and spatial translational control of the meiotic progression of the mammalian oocyte.Cell and Tissue Research 09/2015; DOI:10.1007/s00441-015-2269-6 · 3.57 Impact Factor
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- "CPEB proteins are a family of four paralogs, which regulate the translation of subpopulations of mRNAs in different tissues. They were discovered as orchestrators of oocyte maturation in Xenopus laevis, but recently proved to be more ubiquitous (Theis et al., 2003; Wang and Cooper, 2009) and to have additional functions, including the fine tuning of neuronal plasticity (Wu et al., 1998; Richter, 2007). Structurally , all CPEBs contain an N-terminal regulatory domain and a C-terminal RNA-binding domain, which binds to the consensus mRNA sequences called cytoplasmic polyadenylation elements (CPEs). "
ABSTRACT: Cytoplasmic polyadenylation element binding (CPEB) proteins are translational regulators that are involved in the control of cellular senescence, synaptic plasticity, learning and memory. We have previously found all four known CPEB family members to be transcribed in the mouse hippocampus. Aside from a brief description of CPEB2 in mouse brain, not much is known about its biological role. Hence, the present study aims to investigate CPEB2 expression in mouse brain. With RT-PCR of total mouse brain cDNA, we identified four distinct CPEB2 splice variants. Single-cell RT-PCR showed that CPEB2 is predominantly expressed in neurons of the juvenile and adult brain and that individual cells express different sets of splice variants. Staining of brain slices with a custom-made CPEB2 antibody revealed ubiquitous expression of the protein in many brain regions, including hippocampus, striatum, thalamus, cortex and cerebellum. We also found differential expression of CPEB2 protein in excitatory, inhibitory and dopaminergic neurons. In primary hippocampal cultures, the subcellular localization of CPEB2 in neurons and astrocytes resembled that of CPEB1. Electrophoretic mobility shift assay and RNA co-immunoprecipitation revealed CPEB2 interaction with β-catenin and Ca(2+) /calmodulin-dependent protein kinase II (both established CPEB1 targets), indicating an overlap in RNA binding specificity between CPEB1 and CPEB2. Furthermore, we identified ephrin receptor A4 (EphA4) as a putative novel target of CPEB2. In conclusion, our work identifies CPEB2 splice variants to be differentially expressed among individual cells and across cell types of the mouse hippocampus, and reveals overlapping binding specificity between CPEB2 and CPEB1. This article is protected by copyright. All rights reserved. © 2014 Wiley Periodicals, Inc.Hippocampus 12/2014; 25(5). DOI:10.1002/hipo.22399 · 4.16 Impact Factor
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- "CPEB1 is a key regulator of local dendritic translation and it also facilitates the transport of specifi c mRNAs into dendrites (Richter 2007 ). CPEB1 is phosphorylated in response to the activation of NMDA receptors (NMDARs), which results in polyadenylation and concomitant translation of target mRNAs ( Huang et al. 2002 ) known to participate in dendritic morphogenesis during development and in synaptic plasticity in adulthood ( Richter 2007 ). Using a heterologous reporter system in Xenopus oocytes, we demonstrated that the translation of some DSCAM 3′UTR isoforms is mediated by CPEB. "
ABSTRACT: DSCAMs (Down syndrome cell adhesion molecules) are a group of immunoglobulin-like transmembrane proteins that contain fibronectin III domains. The founding member of the family was isolated in a positional cloning study that sought to identify genes located on chromosome 21 at the locus 21q22.2-q22.3 that is implicated in the neurological and cardiac phenotypes associated with Down's syndrome. In Drosophila, Dscam proteins are involved in neuronal wiring, while in vertebrates, the role of these cell adhesion molecules in neurogenesis, dendritogenesis, axonal outgrowth, synaptogenesis, and synaptic plasticity is only just beginning to be understood. In this chapter, we will review the functions ascribed to the two paralogous proteins found in humans, DSCAM and DSCAML1 (DSCAM-like 1), based on findings in knockout mice. The signaling pathways downstream of DSCAM activation and the role of DSCAM miss-expression in disease will be also discussed, particularly with regard to the intellectual disability in Down's syndrome.Cell Adhesion Molecules: Implications in Neurological Diseases, Edited by Vladimir Berezin and Peter S. Walmod, 10/2014: chapter 11: pages 249-270; Springer., ISBN: 978-1-4614-8089-1