Evolutionary Changes in the Interaction of miRNA With mRNA of Candidate Genes for Parkinson’s Disease

Abstract

Parkinson’s disease (PD) exhibits the second-highest rate of mortality among neurodegenerative diseases. PD is difficult to diagnose and treat due to its polygenic nature. In recent years, numerous studies have established a correlation between this disease and miRNA expression; however, it remains necessary to determine the quantitative characteristics of the interactions between miRNAs and their target genes. In this study, using novel bioinformatics approaches, the quantitative characteristics of the interactions between miRNAs and the mRNAs of candidate PD genes were established. Of the 6,756 miRNAs studied, more than one hundred efficiently bound to mRNA of 61 candidate PD genes. The miRNA binding sites (BS) were located in the 5′-untranslated region (5′UTR), coding sequence (CDS) and 3′-untranslated region (3′UTR) of the mRNAs. In the mRNAs of many genes, the locations of miRNA BS with overlapping nucleotide sequences (clusters) were identified. Such clusters substantially reduced the proportion of nucleotide sequences of miRNA BS in the 5′UTRs, CDSs, and 3′UTRs. The organization of miRNA BS into clusters leads to competition among miRNAs to bind mRNAs. Differences in the binding characteristics of miRNAs to the mRNAs of genes expressed at different rates were identified. Single miRNA BS, polysites for the binding for one miRNA, and multiple BS for two or more miRNAs in one mRNA were identified. Evolutionary changes in the BS of miRNAs and their clusters in 5′UTRs, CDSs and 3′UTRs of mRNA of orthologous candidate PD genes were established. Based on the quantitative characteristics of the interactions between miRNAs and mRNAs candidate PD genes, several associations recommended as markers for the diagnosis of PD.

Identification of Bovine miRNAs with the Potential to Affect Human Gene Expression

“…In recent years, quantitative characteristics of miRNA interactions with the mRNA of target genes have been established and the features of the organization of miRNA BS in mRNA of target genes have been revealed. This opens up new possibilities for regulating gene expression using miRNA ( Aisina et al, 2019 ; Mukushkina et al, 2020 ; Akimniyazova et al, 2021 ; Kamenova et al, 2021 ). In particular, data on fully complementary miRNA and mRNA interactions raise questions about the function of such associations as they are similar to siRNA ( Table 2 ).…”

“…The high predictive advantage of the MirTarget program lies in the fact that it finds BSs for the entire nucleotide sequence of miRNA and determines important quantitative characteristics of the interaction of miRNA with mRNA. This approach in determining the properties of the interaction of exosomal miRNA with mRNA made it possible to reveal fundamentally new properties of miRNA forming in mRNA clusters to reduce the length of the 5′UTR and CDS regions ( Kondybayeva et al, 2018 ; Aisina et al, 2019 ; Mukushkina et al, 2020 ; Akimniyazova et al, 2021 ; Kamenova et al, 2021 ). Studying the interaction of exogenous miRNAs with mRNA genes of humans in silico makes it possible to significantly reduce the material and time costs for determining effective associations of miRNAs and their target genes.…”

piRNA and miRNA Can Suppress the Expression of Multiple Sclerosis Candidate Genes

“…The MirTarget program has proven itself useful in the search for associations of miRNAs and target genes in various diseases [ 37 , 38 , 39 , 40 , 41 , 42 ]. This program makes it possible to determine the quantitative characteristics of these miRNAs with mRNAs, which is very difficult to establish in wet experiments.…”

Editorial: Bioinformatics of Genome Regulation, Volume I

“…org/research-topics/15891/association-between-individualsgenomic-ancestry-and-variation-in-disease-susceptibility). Kamenova et al (2021) analyzed gene expression regulation by miRNA in Parkinson's disease. Zinchenko et al (2021) studied rare hereditary diseases in Russia.…”

“…The approaches for analysis of gene expression regulation in human diseases from the population genetics point of view were highlighted in the Research Topic “ Association Between Individuals’ Genomic Ancestry and Variation in Disease Susceptibility ” at Frontiers in Genetics ( https://www.frontiersin.org/research-topics/15891/association-between-individuals-genomic-ancestry-and-variation-in-disease-susceptibility ). Kamenova et al (2021) analyzed gene expression regulation by miRNA in Parkinson’s disease. Zinchenko et al (2021) studied rare hereditary diseases in Russia.…”