CPEB, or
cytoplasmic polyadenylation element binding protein, is a highly
conserved RNA
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
-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, respon ...
that promotes the elongation of the
polyadenine tail
Polyadenylation is the addition of a poly(A) tail to an RNA transcript, typically a messenger RNA (mRNA). The poly(A) tail consists of multiple adenosine monophosphates; in other words, it is a stretch of RNA that has only adenine bases. In euka ...
of
messenger RNA.
CPEB most commonly activates the target RNA for
translation
Translation is the communication of the Meaning (linguistic), meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The ...
, but can also act as a repressor,
dependent on its
phosphorylation
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, ...
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. 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-kno ...
''
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 ...
;
a role has also been identified in the
spermatogenesis
Spermatogenesis is the process by which haploid spermatozoa develop from germ cells in the seminiferous tubules of the testis. This process starts with the mitotic division of the stem cells located close to the basement membrane of the t ...
of ''
Caenorhabditis elegans
''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...
''.
CPEB is involved in closed-loop regulation of mRNAs that keeps them inactive. The closed-loop structure between the
3'UTR 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 ...
bound to the
5' cap interacts with Maskin bound to CPEB on the
3' UTR creating translationally inactive
transcripts. This translational inhibition is lifted once CPEB is
phosphorylated, 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
Polyadenylation is the addition of a poly(A) tail to an RNA transcript, typically a messenger RNA (mRNA). The poly(A) tail consists of multiple adenosine monophosphates; in other words, it is a stretch of RNA that has only adenine bases. In eu ...
, 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 membrane potential#Cell excitability, electrically excitable cell (biology), cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous ...
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 s ...
'', mice, and humans, contains an
N-terminal domain not found in other isoforms that shows high sequence similarity to
prion
Prions are misfolded proteins that have the ability to transmit their misfolded shape onto normal variants of the same protein. They characterize several fatal and transmissible neurodegenerative diseases in humans and many other animals. It ...
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 consti ...
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 inf ...
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 with the following proteins:
*
PUM2
Pumilio homolog 2 is an RNA-binding protein that in humans is encoded by the ''PUM2'' gene.
Interactions
PUM2 has been shown to interact with the following proteins:
* CPEB
* DAZL
* DAZ1
Deleted in azoospermia 1, also known as DAZ1, is a protei ...
*
PARN
*
GLD-2
*
symplekin
*
eIF4E binding protein
References
RNA-binding proteins
Neuroscience of memory
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