Figure 1.

Approaches to inhibition of miRNA function. (A) Normal function of miRNAs is to suppress translation of the target mRNA with an open reading frame (ORF), or cause mRNA degradation, by guiding RNA-induced silencing complex (RISC) to the 3′ untranslated region (3′UTR) of the mRNA. (B) miRNA inhibitors are antisense miRNA oligonucleotides (AMOs), including 2′-O-methyl modified AMO, antagomir, locked nucleic acid (LNA), phosphorodiamidate morpholino oligonucleotide (PMO) and peptide nucleic acid (PNA), and block miRNA silencing activity by a complimentary binding to the mature miRNA. (C) miRNA is saturated by miRNA sponges that carry tandem multiplex of complementary sequences, which usually imperfectly match the target miRNA and are inserted in the 3′UTR of a reporter gene. (D) mRNA protector functions by a perfect binding to the 3′UTR of a mRNA and protects it from being bound by its miRNA. (E) Loss-of-function of a miRNA is achieved by direct miRNA knockout from the genome. (F) Tissue specific blockage of miRNA activity is achieved by breeding floxed miRNA sponge transgenic mice (with a stop signal flanked by two LoxP sites) with a proper Cre line.