Recognition of the pre-miRNA structure by Drosophila Dicer-1

• DOI: 10.1038/nsmb.2125
• Publication Date: 2011-09-18T18:19:40Z
• Authors: Akihisa Tsutsumi; Tomoko Kawamata; Natsuko Izumi; Hervé Seitz; Yukihide Tomari
• Keywords: Ribonuclease III; 570; 0303 health sciences; MESH: Drosophila Proteins; MESH: RNA Helicases; 540; MESH: Drosophila melanogaster; Substrate Specificity; MicroRNAs; 03 medical and health sciences; Drosophila melanogaster; MESH: Ribonuclease III; Animals; Drosophila Proteins; MESH: Animals; MESH: Substrate Specificity; [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology; MESH: MicroRNAs; RNA Helicases

Drosophila melanogaster has two Dicer proteins with specialized functions. Dicer-1 liberates miRNA-miRNA* duplexes from precursor miRNAs (pre-miRNAs), whereas Dicer-2 processes long double-stranded RNAs into small interfering RNA duplexes. It was recently demonstrated that Dicer-2 is rendered highly specific for long double-stranded RNA substrates by inorganic phosphate and a partner protein R2D2. However, it remains unclear how Dicer-1 exclusively recognize pre-miRNAs. Here we show that fly Dicer-1 recognizes the single-stranded terminal loop structure of pre-miRNAs through its N-terminal helicase domain, checks the loop size and measures the distance between the 3' overhang and the terminal loop. This unique mechanism allows fly Dicer-1 to strictly inspect the authenticity of pre-miRNA structures.