**2. Biogenesis of miRNA**

A microRNA gene can be located in an intron of another gene, in either the sense or antisense orientation. miRNA can be coordinately expressed with its host gene, or it can have its own promoter independent of its host gene (Ozsolak et al., 2008). The biogenesis of miRNA is a complex process as shown in Figure 1. miRNA is first transcribed as a long primary miRNA (pri-miRNA) by RNA polymerase II in the nucleus (Lee et al., 2004). PrimiRNA is structurally similar to mRNA, but contains a stable stem-loop structure (Cai et al., 2004). Recognition of the hairpin and selection of a cleavage site are mediated by DGCR8. Nuclear RNase III (Drosha) then cleaves the pri-miRNA to release the hairpin-shaped precursor miRNA (pre-miRNAs). The pre-miRNA is exported from the nucleus to the cytoplasm by Exportin 5 (Exp5). In the cytoplasm, the pre-miRNA is subsequently cut by cytoplasmic RNase III (Dicer) in complex with Argonaute2 (Ago2) and TRBP, a doublestranded RNA-binding protein. This process cleaves the pre-miRNA hairpins to remove its hairpin loop, resulting in a miRNA duplex with the appropriate length (Gregory et al., 2005; Han et al., 2004; Lee et al., 2003). Normally, one strand of the duplex is then degraded. The mature miRNA are incorporated into an RNA-induced silencing complex (RISC) (Gregory, et al., 2005; Grishok et al., 2001; Hutvagner et al., 2001; Ketting et al., 2001; Maniataki and Mourelatos, 2005). RISC recognizes target mRNAs through full or partial base-pairing interactions between the miRNA and the to "3'-untranslated region (UTR) of the target mRNA. Depending on pairing interactions between miRNAs and their targets, miRNAs suppress their target gene expression by either mRNA cleavage or translational repression. If an mRNA target match perfectly or near-perfectly to the miRNA, the mRNA will be degraded; otherwise, the mRNA will be translationally suppressed (Meister and Tuschl, 2004).
