Regulation of miRNA content. Part 3. Circadian mechanisms. Single nucleotide polymorphisms of microRNA genes

Abstract

The scientific review presents the process of regulation of miRNA content — the association of miRNA expression activity with circadian rhythms of organism functioning and the dependence on the presence of single nucleotide gene polymorphisms. To write the article, information was searched using databases Scopus, Web of Science, MedLine, PubMed, Google Scholar, EMBASE, Global Health, The Cochrane Library, ­CyberLeninka. The article presents the characteristics of the molecular architecture of circadian clocks of mammals, which are due to the action of day and night, light and darkness. It is stated that the violation of circadian rhythms of the organism is associated with the development of obesity, diabetes, depression, cardiovascular pathology, and tumors. It is also known that the violation of the circadian rhythm of liver function leads to the development of metabolic disorders and, in particular, the emergence of non-alcoholic fatty liver disease, diabetes, and obesity. It is emphasized that microRNAs are factors that determine the functioning of circadian rhythm mechanisms, and the expression of some of them is highly dependent on the time of day. The article shows that to date, more than 240 single-nucleotide polymorphisms of genes and rare mutations in pri-, pre- and mature miRNA sequences have been identified. It is known that single nucleotide polymorphisms of genes of the first group (pri- and pre-microRNAs) interfere with the normal process of maturation of microRNAs. Single-nucleotide polymorphisms of genes of the second group (“seed” region) lead to disruption of the interaction of ­microRNAs with target mRNAs. An association between microRNA genetic polymorphisms and various human diseases, including diseases of the hepatobiliary system, has been established. Thus, the activity of miRNA expression determines the functioning of the mechanisms of the circadian rhythm of the mammalian organism, and the expression of some of them is highly dependent on the time of day. The normal process of maturation of miRNAs is hindered by single nucleotide polymorphisms of genes of the first group (pri- and pre-miRNAs). Single nucleotide polymorphisms of genes of the second group lead to disruption of interaction of miRNA with mRNA targets. Circadian rhythm disorders and genetic ­microRNA polymorphisms are associated with the development of various pathological conditions and human di­seases, including diseases of the hepatobiliary system.

Keywords

• microrna, circadian mechanisms, single nucleotide polymorphisms of microrna genes, review