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
Source: PubMed


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. "
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    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
    • "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. "
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    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
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    • "PAPD1 was also reported to uridylate histone mRNA along with PAPD5 to target it for degradation [123] although the actual PAP that uridylates histone mRNA is somewhat controversial [124]. hGLD2 (PAPD4) is a cytoplasmic PAP that polyadenylates short (A)-tailed mRNAs in the cytoplasm [125] [126] and is involved in diverse functions such as embryonic development, cell cycle, germline maturation, synaptic plasticity, learning and memory [126] [127] [128] [129] [130] [131]. hGLD2 also polyadenylates p53 mRNA in the cytoplasm [128] [132]. "
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    ABSTRACT: Almost all eukaryotic mRNAs acquire a poly(A) tail at the 3′-end by a concerted RNA processing event: cleavage and polyadenylation. The canonical PAP, PAPα, was considered the only nuclear PAP involved in general polyadenylation of mRNAs. A phosphoinositide-modulated nuclear PAP, Star-PAP, was then reported to regulate a select set of mRNAs in the cell. In addition, several non-canonical PAPs have been identified with diverse cellular functions. Further, canonical PAP itself exists in multiple isoforms thus illustrating the diversity of PAPs. In this review, we compare two nuclear PAPs, Star-PAP and PAPα with a general overview of PAP diversity in the cell. Emerging evidence suggests distinct niches of target pre-mRNAs for the two PAPs and that modulation of these PAPs regulates distinct cellular functions.
    FEBS Letters 06/2014; 588(14). DOI:10.1016/j.febslet.2014.05.029 · 3.17 Impact Factor
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