RNA binding proteins in epilepsy

Abstract

RNA binding proteins are involved in a diverse array of biological functions including mRNA transport, splicing, localization, stability and translation. Jerky is an RNA binding protein, complexed with mRNAs in neurons, that regulates mRNA utilization and consequently translation. The mouse line defective in the jerky gene shows recurrent seizures; a hallmark of epilepsy. Lack of FMRP (Fragile X Mental Retardation Protein), another RNA binding protein involved in mRNA processing and translation, also results in seizures in mice. This finding is consistent with the high incidence of epilepsy in fragile X syndrome. These two mutant mice are examples of a seizure condition elicited by a deficiency in RNA binding proteins. It is hypothesized that lack of Jerky and FMRP results in the abnormal translation of target-RNAs compromising the development and/or function of neurons. It is known that perturbation of neuronal development/function can result in recurrent seizures. The seizure phenotype of Jerky and FMRP deficient mice raises the possibility that a dysfunction in RNA binding proteins may be a more general disease mechanism in epilepsy.