Microrna

MicroRNAs were first described in 1993; they are short (21 to 23 nucleotides) highly conserved non-coding RNAs (in humans, > 1,200 different miRNA species are currently known) that play an important role in the complex network of gene regulation, especially gene silencing. MicroRNAs regulate gene expression in a highly specific manner at the post-transcriptional level. The biological functions of most microRNAs are currently unknown.

So far, attention regarding miRNA has focused on their role in inhibiting (silencing) gene expression (RNA interference RNAi). RNA interference (RNAi) is an evolutionarily conserved mechanism by which small double-stranded RNA (dsRNA- small interfering RNA) also known as siRNA - inhibit translation or degrade complementary mRNA sequences. Identification of features and enzymatic components of the RNAi pathway has led to the design of highly effective siRNA molecules for laboratory and therapeutic use.

The function of microRNAs in activating gene expression has been mostly overlooked. It has now been shown that the small RNA molecules, whether produced indigenously as microRNAs (miRNAs) or administered exogenously as synthetic dsRNAs, can activate a particular gene in a sequence-specific manner rather than silencing it. This phenomenon is referred to as RNA activation (RNAa). Like RNAi, RNAa targets specific genes through sequence complementarity, with target specificity determined primarily by the 5' end of the saRNA molecule.

However, the time course of RNAa differs greatly from that of RNAi, with induction of gene expression occurring 2-3 days after transfection, as opposed to a few hours for RNAi-mediated suppression, and the effects of RNAa appear to last longer (at least 10-15 days compared to 5-7 days for RNAi).

This results in a paradoxical system of "yin and yang", which describes two originally opposing but complementary principles. Furthermore, it is possible to switch genes that have been switched off by pathogenic influences (silencing) on again in a gene-specific manner using saRNA. These properties of RNAa and RNAi (RNA interference) demonstrate the complexity and the "yin-yang nature" of gene regulation by small double-stranded ncRNA.

1. Chen R et al (2011) Up-regulation of VEGF by small activator RNA in human corpus cavernosum smooth muscle cells. J Sex Med 8: 2773-2780

2. Kuwabara T et al (2004) A small modulatory dsRNA specifies the fate of adult neural stem cells., Cell 116: 779-793.

3. Li LC et al (2006) Small dsRNAs induce transcriptional activation in human cells. Proc Natl Acad Sci U S A 103: 17337-17342

4. Sand et al.( 2009): MicroRNAs and the skin: tiny players in the body`s largest organ. J Dermatol Sci 53: 169-175