3D RNA Interference: RISC–mRNA Cleavage

RISC / Argonaute — 3D

Guide–target complementarity 85%

Argonaute slicer activity 1.0×

mRNA transcription rate 1.0×

mRNA cleaved

mRNA repressed

Strands in transit

Base-pair match

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How it works

A guide strand sits loaded inside the Argonaute protein at the center of RISC (the glowing green core). mRNA strands — chains of nucleotide beads — drift through the scan zone. Each is tested nucleotide-by-nucleotide against the guide's sequence: a near-perfect match lets Argonaute's slicer domain physically cut the backbone in two; a partial match instead stalls the strand in place, blocking a ribosome from translating it, without ever cutting it.

match = complementarity(guide, target)
match ≥ threshold → Argonaute cleaves (backbone cut, halves drift apart)
threshold_repress ≤ match < threshold → translation stalled (repression)
scan_rate ∝ slicer activity

Guide–target complementarity — how closely each incoming strand's sequence matches the loaded guide; raising it makes both cleavage and repression more frequent and shifts the balance toward outright cutting.
Argonaute slicer activity — how fast the complex commits to a cleave/repress decision once a strand is in range.
mRNA transcription rate — how often new mRNA strands are produced and enter the scene from the far side.
Mode — siRNA mode models a highly complementary, cleavage-prone duplex; miRNA mode models the typical partial 3′-UTR match that favors stalling translation instead of cutting.

Real-world relevance: this slicer-vs-stall decision is exactly what determines whether an RNAi therapeutic (e.g. patisiran) destroys its target transcript outright or merely dampens its expression.

RISC / Argonaute core Guide strand mRNA strand Cleaved Repressed / stalled

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