Long double-stranded precursor RNA is cut by the enzyme Dicer into ~21–23 nucleotide duplexes. One strand (passenger) is discarded; the other (guide strand) is loaded into the RISC complex (RNA-induced silencing complex, core protein Argonaute). Guide-loaded RISC scans free-floating mRNA for a complementary sequence. If the match is near-perfect, Argonaute's slicer activity cleaves the target; if the match is only partial (typical of miRNA on a 3′-UTR), RISC instead represses translation without cutting.
P(silence) = f(complementarity)
match ≥ threshold → Argonaute cleaves mRNA
match < threshold → RISC blocks ribosome (repression)
duplex/sec ∝ Dicer rate · RISC loading rate
- Guide–target complementarity — how closely the guide strand's sequence matches the target mRNA; high values favor outright cleavage, lower values favor translational repression instead.
- Dicer processing rate — how fast precursor RNA is diced into duplexes, setting the supply of guide strands entering RISC.
- RISC loading rate — how fast diced duplexes are loaded into Argonaute-RISC and sent out to scan mRNA.
- Mode — siRNA mode assumes an exogenous, highly complementary duplex (cleavage-favoring); miRNA mode assumes an endogenous duplex with imperfect target matching (repression-favoring).
Real-world relevance: this pathway underlies siRNA knockdown experiments and approved RNAi therapeutics (e.g. patisiran), which silence disease genes by hijacking this same Dicer→RISC→target mechanism.