Hippocampal epitranscriptomic (m6A) in human model of Temporal Lobe Epilepsy

Analogous to DNA methylation and protein phosphorylation it is now well understood that RNA is also subject to extensive processing and modification. N6-methyladenosine (m6A) is the most abundant internal RNA modification and regulates RNA fate in several ways including stability and translational efficiency. The role of m6A in both experimental and human epilepsy remains unknown. Here we use transcriptome-wide m6A arrays to obtain a detailed analysis of the hippocampal m6A-ome from human temporal lobe epilepsy samples. We show that epileptic tissue displays disrupted metabolic and autophagic pathways which may be directly linked to m6A-processing. Together our findings indicate that m6A represents a novel layer of gene regulation complexity in epilepsy and may contribute to the pathomechanisms which drive the development and maintenance of hyperexcitable brain networks. The study investigates the m6A methylation differences between epilepsy and non-epilepsy controls. The epilepsy group is further stratified into two subtypes, based on clinical characterisation of either temporal lobe epilepsy with hippocampal sclerosis (sclerotic TLE) or temporal lobe epilepsy without hippocampal sclerosis (non-sclerotic TLE. Sclerotic TLE (n = 7) vs Non-sclerotic TLE (n = 7) vs Non-epilepsy autopsy control (n = 10). Arraystar Human m6A Single Nucleotide Resolution Microarray was used to identify differential methylation patterns across groups Please note that experiments are carried out as dual channel (eg, Cy3 and Cy5-labeled samples hybridized to the same array) but processed as single channel (Cy3 and Cy5 signals are calculated). Each raw file contains both Cy5 (MazF-Digested) and Cy3 (MazF-UnDigested) data, and is linked to the corresponding MazF-Digested sample record.