Nature Reviews Genetics
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Figure 1 | How does RNAi work?
Genetic and biochemical data indicate a possible two-step mechanism for
RNA interference (RNAi): an initiation step and an effector step. a
| In the first step, input double-stranded (ds) RNA is processed into 2123-nucleotide
'guide sequences'. Whether they are single- or double-stranded remains an
open question. An RNA amplification step (shaded box) has been suggested on
the basis of the unusual properties of the interference phenomenon in whole
animals, but this has not been reproduced definitively in vitro.
b | The guide RNAs are incorporated into a nuclease complex, called the
RNA-induced silencing complex (RISC), which acts in the second effector step
to destroy mRNAs that are recognized by the guide RNAs through base-pairing
interactions. We also suggest the incorporation of an active mechanism to
search for homologous mRNAs. (Endo, endonucleolytic nuclease; exo, exonucleolytic
nuclease; recA, homology-searching activity related to E. coli recA.)
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