ABSTRACT
MiRNAs are endogenous small noncoding RNAs ranging from 18 to 23 nucleotides (nt) in length (Cullen 2009). They play important roles in post-transcriptional regulation of gene expression in various biological processes (Scaria et al. 2007). They bind to their complementary sequences on target messenger RNAs (mRNAs) usually at the 3’ untranslated region (3’UTR), resulting in translational repression or target degradation to silence the gene expression (Kusenda et al. 2006; Bartel 2009). The biogenesis and maturation of miRNAs require several steps, including nuclear processing, nuclear export, and cytoplasmic processing (Denli et al. 2004; Gregory et al. 2004; Han et al. 2004; Cai et al. 2006). In brief, the miRNAencoded gene is transcribed in the nucleus and processed into a hairpin-like structure called pre-miRNAs (Gregory et al. 2006), which are subsequently transported to the cytoplasm (Murchison and Hannon 2004) and further cleaved into imperfect miRNA duplexes (Lund and Dahlberg 2006). One of the two strands usually undergoes degradation while the other remains as a mature miRNA, which is usually incorporated into the miRNA-induced silencing complex (miRISC), where the miRNA interacts with its mRNA target and induces gene silence (Pratt and MacRae 2009). The targeting specificity of the miRNA is mainly dependent upon its seed region (the 2-7 nts in relation to the 5’ end of the mature miRNA). Perfect complementation is not absolutely necessary, but if the miRNA displays high degree of complementation with its target mRNA sequence, it may lead to the cleavage of the target mRNA, while a low degree of complementation will result in translational repression of the target gene (Cullen 2006a; Li et al. 2009). This feature provides miRNAs with tolerance for mutations on the target and potentially resolved the drug-resistant problem.
