Study Sheds Light on Dicer's Role in microRNA Biogenesis

New details about how the Dicer enzyme functions to help in the creation of microRNAs are reported in Nature this week. Dicer is well-known for its role in cleaving the double-stranded RNA to create small regulatory RNAs, including miRNAs and short interfering RNAs (siRNAs), but how this processing occurs in humans is poorly understood because structures of human Dicer (Dicer1) in a catalytic state are lacking. Seoul National University researchers have now determined the cryo-electron microscopy structure of Dicer1 bound to precursor miRNA (pre-miRNA) in its cleaving state. The structure reveals the dynamic spatial rearrangements of several domains of Dicer1 during the transition to a catalytic state, explaining how Dicer1 selects its substrates with specificity. The work, the scientists write, will help in the design of siRNAs and other RNAs for RNA interference and offers a molecular framework for understanding Dicer-related diseases in humans.