A brief review on the mechanisms of miRNA regulation

Abstract

MicroRNAs (miRNAs) are a class of short, endogenously-initiated non-coding RNAs that post-transcriptionally control gene expression via either translational repression or mRNA degradation. It is becoming evident that miRNAs are playing significant roles in regulatory mechanisms operating in various organisms, including developmental timing and host-pathogen interactions as well as cell differentiation, proliferation, apoptosis and tumorigenesis. Likewise, as a regulatory element, miRNA itself is coordinatively modulated by multifarious effectors when carrying out basic functions, such as SNP, miRNA editing, methylation and circadian clock. This mini-review summarized the current understanding of interactions between miRNAs and their targets, including recent advancements in deciphering the regulatory mechanisms that control the biogenesis and functionality of miRNAs in various cellular processes.

Figure 1

Pathways of miRNA editing. The segment of the primary transcript (pri-miRNA) contains the mature miRNA sequence (blue) that resides in one of the arms in the stem-loop precursor structure. Editing (highlighted in red dot) starts at the pri-miRNA stage, and the edited pri-miRNAs may not be processed into precursor miRNA (pre-miRNA). The canonical biogenesis pathway of miRNAs (black arrows; the excised RNA fragments during miRNA biogenesis are indicated with dashed arrows) and the possible miRNA editing events (orange arrows) both happen in the cytosol where pre-miRNA may be subject to further editing events, resulting in the identification of different mRNA target (mRNA’).

Figure 2

miRNA gene expression affected by methylation. The degree of methylation in the upstream sequence of miRNAs is critical; hypermethylation (highlighted in red) and hypomethylation of neighboring CpG islands (horizontal green bars) repress and activate miRNA genes (blue arrow), respectively.