Overview of host miRNA properties and their association with epigenetics, long non-coding RNAs, and Xeno-infectious factors

Abstract

MicroRNA-derived structures play impressive roles in various biological processes. So dysregulation of miRNAs can lead to different human diseases. Recent studies have extended our comprehension of the control of miRNA function and features. Here, we overview some remarkable miRNA properties that have potential implications for the miRNA functions, including different variants of a miRNA called isomiRs, miRNA arm selection/arm switching, and the effect of these factors on miRNA target selection. Besides, we review some aspects of miRNA interactions such as the interaction between epigenetics and miRNA (different miRNAs and their related processing enzymes are epigenetically regulated by multiple DNA methylation enzymes. moreover, DNA methylation could be controlled by diverse mechanisms related to miRNAs), direct and indirect crosstalk between miRNA and lnc (Long Non-Coding) RNAs as a further approach to conduct intercellular regulation called "competing endogenous RNA" (ceRNA) that is involved in the pathogenesis of different diseases, and the interaction of miRNA activities and some Xeno-infectious (virus/bacteria/parasite) factors, which result in modulation of the pathogenesis of infections. This review provides some related studies to a better understanding of miRNA involvement mechanisms and overcoming the complexity of related diseases that may be applicable and useful to prognostic, diagnostic, therapeutic purposes and personalized medicine in the future.

Keywords: Arm selection; DNA methylation; IsomiR; LncRNA; MicroRNA; Xeno-infection.

Fig. 1

MiRNA properties. a IsomiRs as miRNA variants are categorized into three main types, including 3′ isomiR, 5′ isomiR, and polymorphic isomiR that they can affect a miRNA at the target level to select different mRNA (b) Arm selection is a feature of miRNA that can affect target selection of miRNA by isomiRs and it can occur in three common steps, including (d) 5p arms of a miRNA duplex selected as a guide strand to incorporates into the RISC complex., (e) 3p arms of a miRNA duplex may be selected as a guide strand to incorporates into the RISC complex., and (f) occasionally, two arms of a miRNA duplex can be used as guide RNA and incorporate into the RISC complexes with different target mRNAs. Note: the guide strand of a miRNA has weaker binding to Ago protein. However, the passenger strand has a tighter binding capacity to Ago protein. c Arm selection of a miRNA can be changed in different conditions that it termed as arm switching

Fig. 2

MiRNA and methylation: miRNA and DNA methylation have interaction with each other in two ways, including the effects of miRNA on methylation and vice versa. DNA methylation can affect 1) miRNA-related gene or 2) promoter region of miRNA processing enzymes and cofactors such as TRBP and DGCR8 and also can affect CPG sites of Drosha gene body. Mutually, a miRNA can affect DNA methylation in two ways, including 1) it can target genes of DNA methylation-related enzymes such as DNMTs, TETs, MECP2, and MBDs, and leads to hyper- or hypo-methylation of different genes. 2) Also, miRNA processing-related enzymes can directly or indirectly affect DNA methylation through recruiting DNMTs to CpG sites in the genome or at gene levels

Fig. 3

Interaction between miRNA and lncRNA. There are three states of collaboration among miRNAs and lncRNAs: a miRNA can bind to its binding site of lncRNA and weak lncRNA stability. b LncRNA and miRNA can compete with each other to binding to target mRNA. c Also, lncRNA can affect the binding of miRNA to target mRNA through sponging the miRNA. However, sometimes miRNA can decoy from lncRNA and bind to related mRNA