CPEB

CPEB, or cytoplasmic polyadenylation element binding protein, is a highly conserved RNA-binding protein that promotes the elongation of the polyadenine tail of messenger RNA.^[1] CPEB most commonly activates the target RNA for translation, but can also act as a repressor,^[2] dependent on its phosphorylation state.^[3] In animals, CPEB is expressed in several alternative splicing isoforms that are specific to particular tissues and functions, including the self-cleaving Mammalian CPEB3 ribozyme. CPEB was first identified in Xenopus oocytes and associated with meiosis;^[1] a role has also been identified in the spermatogenesis of Caenorhabditis elegans.^[4]

Role in memory

Drosophila Orb2 binds to genes implicated in long-term memory. An isoform of CPEB found in the neurons of the sea slug Aplysia californica, as well as in Drosophila, mice, and humans, contains an N-terminal domain not found in other isoforms that shows high sequence similarity to prion proteins. Experiments with the Aplysia isoform expressed in yeast reveal that CPEB has a key property associated with prions: it can cause other proteins to assume alternate protein conformations that are heritable in successive generations of yeast cells. Furthermore, the functional RNA-binding form of the CPEB protein may be the prion-like state.^[5] These observations have led to the suggestion that long-lasting bistable prionlike proteins play a role in the formation of long-term memory.^[6]

References

1. ^ ^{a b} Hake, L.E., and Richter, J.D. (1994). CPEB is a specificity factor that mediates cytoplasmic polyadenylation during Xenopus oocyte maturation. Cell 79, 617–627.
2. ^ de Moor, C.H., and Richter, J.D. (1999). Cytoplasmic polyadenylation mediate masking and unmasking of cyclin B1 mRNA. EMBO J. 18, 2294–2303.
3. ^ Mendez, R., Barnard, D., and Richter, J.D. (2002). Differential mRNA translation and meiotic progression require Cdc2-mediated CPEB destruction. EMBO J. 21, 1833–1844.
4. ^ Luitjens C, Gallegos M, Kraemer B, Kimble J, Wickens M. (2000). CPEB proteins control two key steps in spermatogenesis in C. elegans. Genes Dev 14(20):2596-609.
5. ^ Si K, Lindquist S, Kandel ER. (2003). A Neuronal Isoform of the Aplysia CPEB Has Prion-Like Properties. Cell 115: 879-91.
6. ^ Shorter J, Lindquist S (2005). "Prions as adaptive conduits of memory and inheritance". Nat Rev Genet 6 (6): 435-50. doi:10.1038/nrg1616 PMID 15931169

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