Dicer-related helicase 3 forms an obligate dimer for recognizing 22G-RNA.

Dicer is a specialized nuclease that produces RNA molecules of specific lengths for use in gene silencing pathways. Dicer relies on the correct measurement of RNA target duplexes to generate products of specific lengths. It is thought that Dicer uses its multidomain architecture to calibrate RNA product length. However, this measurement model is derived from structural information from a protozoan Dicer, and does not account for the helicase domain present in higher organisms. The Caenorhabditis elegans Dicer-related helicase 3 (DRH-3) is an ortholog of the Dicer and RIG-I family of double-strand RNA activated ATPases essential for secondary siRNA production. We find that DRH-3 specifies 22 bp RNAs by dimerization of the helicase domain, a process mediated by ATPase activity and the N-terminal domain. This mechanism for RNA length discrimination by a Dicer family protein suggests an alternative model for RNA length measurement by Dicer, with implications for recognition of siRNA and miRNA targets.