miRNAs clamp down on gene expression by cleavage or translational inhibition of mRNAs through binding to complementary regions in the 3′-untranslated region (3’-UTR) of their targets. Although, greatest studies into miRNA function has located for sites in 3′ UTRs, some investigations show that targeting can happen in 5′ UTRs and coding sequence (CDS)[1, 2].

miRNA biosynthesis is mainly mediated by two RNase III-proteins; the initially transcribed pri-miRNA is processed by Drosha to pre-miRNA that is next exported to the cytoplasm to be further processed to double-stranded 21-23 nt long mature miRNA by Dicer. In some cases, only one of the two strands of the mature miRNA, known as guide strand, associates with the RNA-induced silencing complex (RISC) and directs it to target mRNAs by base pairing; whereas, in other cases both strands can do this (Figure 1). In plants, the homology between miRNA and mRNA is extensive and leads to mRNA degradation. However, in animals, the complementarity is mostly located to nucleotides 2-8 at the 5’ end of miRNA (seed region)[3-5]. Concepts of miRNA function are summarized in Figure.

 

 

miRNA gene transcription, biogenesis and function. Several transcription factors (TF) control miRNA gene transcription positively or negatively. miRNAs are transcribed by RNA polymerase II to yield pri-miRNA which is processed by Drosha to pre-miRNA. Pri-miRNAs are  then exported to the cytoplasm to be further processed into double-stranded 21-23 nt long mature miRNA by Dicer. Mature miRNA associates with the RNA-induced silencing complex (RISC) and directs it to target mRNAs by base pairing.

A single miRNA can suppress the expression of hundreds of genes, therefore controlling several molecular processes. Multiplicity of miRNA targets, a routine process of miRNA function includes the limited suppression of numerous mRNAs in a biological pathway by a single miRNA. This mechanism decreases the requirement on a single miRNA-mRNA interaction and rises the strength of the gene controlling system. miRNA buffering effect, miRNAs may target factors which activate or inhibit a certain process, thus protecting that process from environmental oscillations.

 


1.    Kloosterman WP, Wienholds E, Ketting RF et al. Substrate requirements for let-7 function in the developing zebrafish embryo, Nucleic Acids Res 2004;32:6284-6291.
2.    Lytle JR, Yario TA, Steitz JA. Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5' UTR as in the 3' UTR, Proc Natl Acad Sci U S A 2007;104:9667-9672.
3.    Davis-Dusenbery BN, Hata A. Mechanisms of control of microRNA biogenesis, J Biochem 2010;148:381-392.
4.    Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay, Nat Rev Genet 2010;11:597-610.
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