Dicer, Argonaute, and the RISC complex
/ DY-ser; AR-go-nawt; risk /
If RNA interference is a search-and-destroy operation, it needs two pieces of equipment: a shredder to cut the input into bite-sized guides, and a hunter that takes one guide and goes looking for matching targets. Dicer is the shredder, Argonaute is the hunter, and the loaded hunter-plus-guide assembly is called RISC.
Dicer is an enzyme that grabs a long double-stranded RNA (or a folded microRNA precursor) and chops it into short pieces about 21 to 23 nucleotides long — neat little double-stranded RNAs with a characteristic two-base overhang. One strand of each piece is then handed to Argonaute, the heart of the RNA-induced silencing complex, RISC. Argonaute clamps onto the guide strand and uses it as a search query: it scans messenger RNAs and pairs the guide against them. If the match is good, Argonaute acts: some Argonaute proteins are slicers that cut the target RNA in half (typical of siRNA-driven silencing), while in microRNA-driven silencing RISC more often just blocks translation and triggers decay. The guide is reusable, so one loaded RISC can silence many target molecules.
These two proteins are the shared engine under both the siRNA and microRNA pathways — the same Dicer-then-Argonaute logic, fed by different sources of small RNA. Understanding RISC also explains the medicines now in clinics: small interfering RNA drugs are simply synthetic guides designed to load into a patient's own RISC and silence a disease-causing gene. The deep tools (designed siRNAs and CRISPR guide RNAs as engineering) are detailed elsewhere; here we meet the natural machine itself.
Step by step: a long double-stranded RNA enters; Dicer cuts it into 22-base pieces; one strand loads into Argonaute to form RISC; RISC scans the cell, finds a matching mRNA, base-pairs to it, and Argonaute slices it — gene silenced.
Dicer chops, Argonaute carries the guide, and RISC finds and silences the matching message.
Not every Argonaute can slice. Humans have several Argonaute proteins, and only one of them retains the cutting activity; the others silence by blocking and recruiting decay factors instead. So loading a guide into RISC does not always mean the target is cut in two.