Structure of the human DICER-pre-miRNA complex in a dicing state II

Dicer plays a key role in small RNA biogenesis by processing double-stranded RNAs (dsRNAs). Human DICER (hDICER) is specialized in processing of small hairpins such as pre-microRNAs (pre-miRNAs) with a limited activity towards long dsRNAs, unlike its homologs in lower eukaryotes and plants which cleave long dsRNAs. While the mechanism of long dsRNA cleavage has been well documented, our understanding of pre-miRNA processing is limited due to lack of the structure of hDICER in a catalytic state. Here we report the cryo-electron microscopy structure of hDICER bound to pre-miRNA in a dicing state, uncovering the structural basis for pre-miRNA processing. AQ-seq (bias-minimized sRNA-seq) libraries were constructed using total RNAs as described in our previous study (Kim et al., 2019).