CPEB, or cytoplasmic polyadenylation element binding protein, is a highly conserved RNA-binding

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that promotes the elongation of the polyadenine tail of messenger RNA. CPEB most commonly activates the target RNA for

translation Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...

, but can also act as a repressor, dependent on its phosphorylation state. 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 The mammalian CPEB3 ribozyme is a self cleaving non-coding RNA located in the second intron of the CPEB3 gene which belongs to a family of genes regulating messenger RNA polyadenylation. This ribozyme is highly conserved and found only in mamma ...

. CPEB was first identified in ''

Xenopus ''Xenopus'' () (Gk., ξενος, ''xenos''=strange, πους, ''pous''=foot, commonly known as the clawed frog) is a genus of highly aquatic frogs native to sub-Saharan Africa. Twenty species are currently described within it. The two best-know ...

oocyte An oocyte (, ), oöcyte, or ovocyte is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The femal ...

s and associated with

meiosis Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately r ...

; a role has also been identified in the spermatogenesis of '' Caenorhabditis elegans''. CPEB is involved in closed-loop regulation of mRNAs that keeps them inactive. The closed-loop structure between the

3'UTR In molecular genetics, the three prime untranslated region (3′-UTR) is the section of messenger RNA (mRNA) that immediately follows the translation termination codon. The 3′-UTR often contains regulatory regions that post-transcriptionally ...

and

5'UTR The 5′ untranslated region (also known as 5′ UTR, leader sequence, transcript leader, or leader RNA) is the region of a messenger RNA (mRNA) that is directly upstream from the initiation codon. This region is important for the regulation of t ...

inhibits translation. This has been observed in ''

Xenopus laevis The African clawed frog (''Xenopus laevis'', also known as the xenopus, African clawed toad, African claw-toed frog or the ''platanna'') is a species of African aquatic frog of the family Pipidae. Its name is derived from the three short claws ...

'' in which

eIF4E Eukaryotic translation initiation factor 4E, also known as eIF4E, is a protein that in humans is encoded by the ''EIF4E'' gene. Structure and function Most eukaryotic cellular mRNAs are blocked at their 5'-ends with the 7-methyl-guanosine f ...

bound to the 5' cap interacts with Maskin bound to CPEB on the

3' UTR In molecular genetics, the three prime untranslated region (3′-UTR) is the section of messenger RNA (mRNA) that immediately follows the translation termination codon. The 3′-UTR often contains regulatory regions that post-transcriptionally ...

creating translationally inactive transcripts. This translational inhibition is lifted once CPEB is

phosphorylated In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...

, displacing the Maskin binding site, allowing for the

polymerization In polymer chemistry, polymerization (American English), or polymerisation (British English), is a process of reacting monomer molecules together in a chemical reaction to form polymer chains or three-dimensional networks. There are many fo ...

of the PolyA tail, which can recruit the translational machinery by means of PABP. However, it is important to note that this mechanism has been under great scrutiny.

Role in memory

Drosophila Orb2 binds to genes implicated in long-term memory. An isoform of CPEB found in the

neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. ...

s of the sea slug '' Aplysia californica'', as well as in ''

Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many speci ...

'', 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 Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constit ...

reveal that CPEB has a key property associated with prions: it can cause other proteins to assume alternate protein conformations that are

heritable Heredity, also called inheritance or biological inheritance, is the passing on of traits from parents to their offspring; either through asexual reproduction or sexual reproduction, the offspring cells or organisms acquire the genetic informa ...

in successive generations of yeast cells. Furthermore, the functional RNA-binding form of the CPEB protein may be the prion-like state. These observations have led to the suggestion that long-lasting bistable prionlike proteins play a role in the formation of long-term

memory Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembered ...

. It has been suggested that "both memory storage and its underlying synaptic plasticity are mediated by the increase in. . .CPEB."

Interactions

CPEB has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with the following proteins: * PUM2 * PARN *

GLD-2 GLD-2 (which stands for Germ Line Development 2) is a cytoplasmic poly(A) polymerase (cytoPAPs) which adds successive AMP monomers to the 3’ end of specific RNAs, forming a poly(A) tail, which is a process known as polyadenylation. For RNA ...

* symplekin * eIF4E binding protein

References

RNA-binding proteins Neuroscience of memory {{protein-stub