“MicroRNA epigenetic signatures” (Piletic & Kunej, 2016) in epilepsy

        Post-translational modifications in epigenetics, such as methylation and acetylation, have always been discussed, but on the other hand, the active role of microRNAs (miRNAs) has not been explained in such detail. miRNAs are short non-coding RNAs that participate as regulators of gene expression. Klara Piletic and Tanja Kunej describe 63 miRNA genes that are epigenetically regulated in association with 21 diseases, such as cardiovascular disease, rheumatoid arthritis, autism, gastric, cervical, ovarian, prostate and bladder cancer. Temporal lope epilepsy (TLE) is included in these diseases.

          MiRNAs are approximately 22 nucleotides long, and there are currently more than 460 human miRNAs known.  They are transcribed by RNA polymerase II (Pol II). miRNAs target messenger RNAs (mRNAS) and degrade them. miRNA is non coding RNA, that is transcribed and is exported from the nucleus. It is then cut by a Dicer protein down to 22 nucleotides and then loaded into the Argonaut complex, where it can inhibit gene translation and act to degrade other RNAs.

http://www.nature.com/leu/journal/v26/n3/images/leu2011344f1.jpg

In temporal lobe epilepsy, the following miRNAs genes are epigenetically regulated: miR-27a, miR-193a-5p, miR-486, miR-618, miR-133a-1, miR-151, miR-191, miR-375, miR-411, miR-342, miR-34a, miR-627 and miR-576. Patients that suffer from TLE, “can display hippocampal sclerosis, which is a histopathologic abnormality including segmental neuron loss as well as other changes” (2016). DNA hyper methylation plays a major role in this condition, but so does miRNA, that “plays a role in the pathophysiology of TLE” (2016).  

           

References:

Piletic, K. & Kunej, T. (2016). MicroRNA epigenetic signatures in human disease. Archives of Toxicology, 90(2405-2419).