Mode of action (mechanism)
Current and further research
Long dsRNAs are processed by Dicer to give ∼21 bp siRNA duplexes, one strand of which is then incorporated into the RNA induced silencing complex (RISC). Efforts in the Drosophila and C. elegans systems to clone these short non-coding RNAs based on their size led to the surprising discovery that not only these organisms, but also vertebrates, express over 200 genomically encoded ∼21 nucleotide RNAs. These RNAs, which are now termed microRNAs (miRNAs), are predicted to form part of one strand of an imperfect precursor RNA hairpin structure of between 60 and 90 nucleotides in length. This contrasts with Small interfering RNA (siRNAs), which are invariably derived from long dsRNAs. In addition, while miRNAs are by definition of endogenous origin, siRNAs can be endogenous or exogenous.
Although many different miRNAs have been reported in a range of species, very few have as yet been assigned a function. Exceptions include not only let-7 and lin-4 in C. elegans but also two miRNAs termed bantam and miR-14 in Drosophila, miR-171 in Arabidopsis and miR-23 in human cells. As in the case of let-7 and lin-4, these miRNAs are expressed in a developmentally regulated manner and inhibit the expression of target mRNAs bearing complementary sequences.