Introduction
RNA interference (RNAi) represents a highly conserved cellular mechanism to specifically regulate eukaryotic gene expression either by inducing sequence- specific degradation of complementary mRNA or by inhibiting its translation (reviewed in Hannon, 2002; Hutvagner & Zamore, 2002). RNAi is triggered by two classes of small RNAs: one class, called siRNA (small interfering RNA), can be derived from longer double-stranded RNAs that are transcribed from different kinds of vector or introduced directly into cells by transfection, whereas the second class, miRNA (microRNA), is processed from stem-loop precursors that are encoded within the host genome (Elbashir et al., 2001; Ambros et al., 2003).
Non-coding miRNAs negatively regulate the expression of genes at the post-transcriptional level through the RNAi pathway (Bartel, 2004). The first miRNA, lin-4, was discovered in 1993 by Ambros and colleagues (Lee et al., 1993) in a study of developmental timing in the nematode worm C. elegans and soon led to the identification of the first miRNA target lin-14 (Wightman et al., 1993). The second miRNA discovered, let-7, is involved in regulation of intracellular signal transduction and has recently been shown to inhibit expression of let-60, the nematode RAS homolog (Johnson et al., 2005). Hundreds of miRNAs have been identified in flies, worms, plants, fish, and mammals by cloning of size-fractionated RNAs or bioinformatic prediction strategies (Lagos-Quintana et al., 2001; Llave et al., 2002; Lim et al., 2003a, 2003b; Watanabe et al., 2005).