Dicer structure and function: conserved and evolving features

RNase III Dicer produces small RNAs guiding sequence-specific regulations, with important biological roles in eukaryotes. Major Dicer-dependent mechanisms are RNA interference (RNAi) and microRNA (miRNA) pathways, which employ distinct types of small RNAs. Small interfering RNAs (siRNAs) for RNAi are produced by Dicer from long double-stranded RNA (dsRNA) as a pool of different small RNAs. In contrast, miRNAs have specific sequences because they are precisely cleaved out from small hairpin precursors. Some Dicer homologs efficiently generate both, siRNAs and miRNAs, while others are adapted for biogenesis of one small RNA type. Here, we review the wealth of recent structural analyses of animal and plant Dicers, which have revealed how different domains and their adaptations contribute to substrate recognition and cleavage in different organisms and pathways. These data imply that siRNA generation was Dicer's ancestral role and that miRNA biogenesis relies on derived features. While the key element of functional divergence is a RIG-I-like helicase domain, Dicer-mediated small RNA biogenesis also documents the impressive functional versatility of the dsRNA-binding domain.

Automated summary

RNase III Dicer plays important biological roles in eukaryotes by generating small RNAs for sequence-specific regulations. RNA interference (RNAi) and microRNA (miRNA) pathways are the major Dicer-dependent mechanisms, which produce distinct types of small RNAs. Structural analyses of animal and plant Dicers have revealed the contributions of different domains to substrate recognition and cleavage, highlighting the ancestral role of siRNA generation and the derived features of miRNA biogenesis. The functional divergence is mainly attributed to a RIG-I-like helicase domain, while the dsRNA-binding domain showcases the impressive functional versatility in Dicer-mediated small RNA biogenesis.