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. 2006;2006(4):69616.
doi: 10.1155/JBB/2006/69616.

MicroRNAs in gene regulation: when the smallest governs it all

Dominique L Ouellet  1 , Marjorie P Perron, Lise-Andrée Gobeil, Pierre Plante, Patrick Provost
Affiliations

MicroRNAs in gene regulation: when the smallest governs it all

Dominique L Ouellet et al. J Biomed Biotechnol. 2006.

Abstract

Encoded by the genome of most eukaryotes examined so far, microRNAs (miRNAs) are small approximately 21-nucleotide (nt) noncoding RNAs (ncRNAs) derived from a biosynthetic cascade involving sequential processing steps executed by the ribonucleases (RNases) III Drosha and Dicer. Following their recent identification, miRNAs have rapidly taken the center stage as key regulators of gene expression. In this review, we will summarize our current knowledge of the miRNA biosynthetic pathway and its protein components, as well as the processes it regulates via miRNAs, which are known to exert a variety of biological functions in eukaryotes. Although the relative importance of miRNAs remains to be fully appreciated, deregulated protein expression resulting from either dysfunctional miRNA biogenesis or abnormal miRNA-based gene regulation may represent a key etiologic factor in several, as yet unidentified, diseases. Hence is our need to better understand the complexity of the basic mechanisms underlying miRNA biogenesis and function.

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Figures

Figure 1
Figure 1
mRNA regulation mediated by microRNAs (miRNAs). miRNA genes are transcribed by RNA polymerase II into primary miRNAs (pri-miRNAs), which are processed by Drosha, acting in concert with DiGeorge syndrome critical region 8 (DGCR8) protein within the microprocessor complex, into ∼60 to 70 nt miRNA precursors (pre-miRNAs). Following export via exportin-5, pre-miRNAs are cleaved by Dicer, acting in concert with transactivating response RNA-binding protein (TRBP) within the pre-miRNA processing complex, to generate an imperfect miRNA:miRNA* duplex of ∼ 21 to 23 nt. After a strand selection/separation process, the mature miRNA is loaded into an effector miRNA-containing ribonucleoprotein (miRNP) complex that will recognize and mediate repression or cleavage of specific mRNAs. Synthetic small interfering RNAs (siRNAs) can be introduced into cells and be incorporated into the endogenous miRNA-guided RNA silencing machinery to mediate cleavage of the targeted mRNA.
Figure 2
Figure 2
Some peculiarities of the major protein components of the microRNA-guided RNA silencing.
Figure 3
Figure 3
Recognition of the lin-41 mRNA by let-7 in C elegans. The lin-41 3′NTR contains two let-7 complementary sites (LCS) separated by a 27 nt sequence that seems to be important in target recognition [143]. The miRNA seed consists in a perfect pairing of nucleotides 2 to 8 of the miRNA.
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