ELP4
Encyclopedia
Elongation protein 4 homolog (S. cerevisiae), also known as ELP4, is a protein
which in humans is encoded by the ELP4 gene
.
complex that associates directly with RNA polymerase II
during transcriptional elongation
. The human gene can partially complement sensitivity phenotypes of yeast ELP4 deletion mutants. Alternatively spliced variants that encode different protein isoforms have been described but the full-length nature of only one has been determined.
, namely Rolandic epilepsy
. This is the first gene to be linked with rolandic epilepsy.
(HAT) activity which makes DNA more accessible for transcription. The lack of the Elp4/5/6 led to no HAT activity. The importance of HAT activity is the initiation of transcription as well as its assistance of RNA polymerase II
in transcription elongation through chromatin and acetyl-CoA dependent pathways. Although Rolandic epilepsy (RE), which has been observed as autosomal dominant with high penetrance, develops around age 3 and disappears by age 12 there are serious problems that need to be addressed that occur while a child has RE. One of the major problems that can arise from RE is cognitive impairment. Though the cognitive impairment seen in Rolandic Epilepsy is of unclear etiology, one contributing factor may be increased glucose uptake in cortical areas, most notably in the associative cortex. These changes in glucose uptake may somehow disrupt the learning process and prevents the child form making the associations necessary to learn new things, which is how most human learning is achieved. Other factors which may contribute to cognitive impairment include seizure frequency, abnormal electrical activity in between seizures, and medication side effects, to only name a few.
The Elongator Protein Complex (ELP) is what regulates the growth of cortical projection neurons. This means that it helps cortical neurons to exhibit dendrite branching and radial migration of neurons to form the close knit neural network of the cerebral cortex. If ELP is not working properly or is not being expressed at the correct levels (too low) then the neurons in that region in particular would not be properly situated in relation to each other for proper brain activity. The expression of ELP and the fourth sub-unit (ELP4) in particular is the cause of Rolandic epilepsy and possibly other cognitive impairment later in life if the condition is severe enough or if it is not treated effectively.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
which in humans is encoded by the ELP4 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
This gene encodes a component of the six subunit elongator complex, a histone acetyltransferaseHistone acetyltransferase
Histone acetyltransferases are enzymes that acetylate conserved lysine amino acids on histone proteins by transferring an acetyl group from acetyl CoA to form ε-N-acetyl lysine....
complex that associates directly with RNA polymerase II
RNA polymerase II
RNA polymerase II is an enzyme found in eukaryotic cells. It catalyzes the transcription of DNA to synthesize precursors of mRNA and most snRNA and microRNA. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase...
during transcriptional elongation
Elongation factor
Elongation factors are a set of proteins that facilitate the events of translational elongation, the steps in protein synthesis from the formation of the first peptide bond to the formation of the last one.Elongation is the most rapid step in translation:...
. The human gene can partially complement sensitivity phenotypes of yeast ELP4 deletion mutants. Alternatively spliced variants that encode different protein isoforms have been described but the full-length nature of only one has been determined.
Clinical significance
In a study published in February 2009, researcher linked this gene to the most common form of human epilepsyEpilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
, namely Rolandic epilepsy
Rolandic epilepsy
In neurology and pediatrics, benign rolandic epilepsy or benign epilepsy with centrotemporal spikes is the most common epilepsy syndrome in childhood. Most children will outgrow the syndrome , hence the label benign...
. This is the first gene to be linked with rolandic epilepsy.
Background
It has been found that children with Rolandic epilepsy have a mutation of gene coding for the Elongator Protein Complex 4, which is involved in transcription and tRNA modification. Furthermore Elp4 is needed for histone acetyltransferaseHistone acetyltransferase
Histone acetyltransferases are enzymes that acetylate conserved lysine amino acids on histone proteins by transferring an acetyl group from acetyl CoA to form ε-N-acetyl lysine....
(HAT) activity which makes DNA more accessible for transcription. The lack of the Elp4/5/6 led to no HAT activity. The importance of HAT activity is the initiation of transcription as well as its assistance of RNA polymerase II
RNA polymerase II
RNA polymerase II is an enzyme found in eukaryotic cells. It catalyzes the transcription of DNA to synthesize precursors of mRNA and most snRNA and microRNA. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase...
in transcription elongation through chromatin and acetyl-CoA dependent pathways. Although Rolandic epilepsy (RE), which has been observed as autosomal dominant with high penetrance, develops around age 3 and disappears by age 12 there are serious problems that need to be addressed that occur while a child has RE. One of the major problems that can arise from RE is cognitive impairment. Though the cognitive impairment seen in Rolandic Epilepsy is of unclear etiology, one contributing factor may be increased glucose uptake in cortical areas, most notably in the associative cortex. These changes in glucose uptake may somehow disrupt the learning process and prevents the child form making the associations necessary to learn new things, which is how most human learning is achieved. Other factors which may contribute to cognitive impairment include seizure frequency, abnormal electrical activity in between seizures, and medication side effects, to only name a few.
The Elongator Protein Complex (ELP) is what regulates the growth of cortical projection neurons. This means that it helps cortical neurons to exhibit dendrite branching and radial migration of neurons to form the close knit neural network of the cerebral cortex. If ELP is not working properly or is not being expressed at the correct levels (too low) then the neurons in that region in particular would not be properly situated in relation to each other for proper brain activity. The expression of ELP and the fourth sub-unit (ELP4) in particular is the cause of Rolandic epilepsy and possibly other cognitive impairment later in life if the condition is severe enough or if it is not treated effectively.