Circular RNAs as a novel layer of regulatory mechanism in multiple sclerosis.


Department of Neurology, Laboratory of Neuroimmunology, Collegium Medicum, University of Warmia and Mazury, Olsztyn, Poland. Electronic address: [Email]


Multiple sclerosis (MS) is believed to be an autoimmune disease of the central nervous system (CNS) in which autoreactive immune cells recognizing myelin antigens lead to demyelination and axonal injury. Mechanisms inducing and controlling the pathogenesis of MS have not been fully elucidated. Recent studies suggest an important role of epigenetic processes during the development of MS. One of the most significant discoveries in the field of epigenetic contribution to immune response has been the recognition of a group of microRNAs (miRNAs). These single-stranded non-coding RNA molecules regulate the expression of genes encoding proteins and have already been shown to be involved in pathogenesis of MS. Some miRNAs enhance generation of pro-inflammatory immune cells by promoting Th1 and Th17 pathways and others contribute to regulatory and tissue repair processes. The miRNA-dependent controlling process of autoimmune reactions is highly complex because of miRNA redundancy and multitarget nature of most of these molecules. Recently it was discovered that circular RNAs (circRNA) representing a new class of RNA possess a unique ability to control miRNAs by blocking their activity. CircRNAs are called natural miRNA "sponges" as the single circRNA molecule is able to neutralize several miRNAs and thus might determine the availability of miRNAs for their posttranscription regulation. Thus, circRNAs emerged as critical factors in epigenetic regulation of many human diseases including MS. In addition, in contrary to other RNA species they are very stable in the blood and other biological fluids and thus might be considered as a candidate for a biomarker of MS.

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