(A) CHR2 interacted with SE accessed pri-miRNAs and remodelled their RNA secondary structures, preventing the formation of hairpin structures and subsequently inhibiting the pri-miRNA processing by DCL1 that is required to generate mature miRNAs. (B) miRNA target sites were not structurally accessible for miRISC binding prior to cleavage in living cells. (C) The single-strandedness of the two nucleotides immediately downstream of the target site, TAM, is capable of triggering miRNA cleavage.