Dicer2

Dicer-2, or Dcr-2, is an RNase III family endoribonuclease that participates in the small interfering RNA (siRNA) branch of RNA interference in Drosophila and many other invertebrates. It cleaves long double-stranded RNA into short interfering RNA duplexes of about 21–22 nucleotides, initiating RISC-mediated silencing.

Dcr-2 is a multi-domain protein that typically includes a helicase/ATPase domain, a PAZ-like domain for dsRNA end recognition, two RNase III catalytic domains, and a double-stranded RNA-binding domain. This domain organization supports dsRNA processing and product handoff to downstream factors.

In the siRNA pathway, Dcr-2 works with the dsRNA-binding protein R2D2 to load the resulting siRNA duplexes into Argonaute2-containing RISC. One strand becomes the guide RNA while the other is discarded; the guide directs degradation of complementary transcripts.

In Drosophila, Dcr-2 is central to exogenous RNAi and antiviral defense, contrasting with Dcr-1 which processes microRNA precursors in partnership with Loquacious. The two Dicers distinguish the miRNA and siRNA pathways, though cross-talk exists.

Homologs of Dcr-2 are found in many insects and some other invertebrates, reflecting evolution of the RNAi machinery. Disruption of Dcr-2 impairs RNAi efficacy and antiviral responses in organisms that rely on exogenous dsRNA sensing.