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Rna-induced Silencing Complex
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STRANDS

The RNA Endonuclease Dicer plays a role in aiding RISC action by providing the initial RNA material to activate the complex as well as the first RNA substrate molecule.
When Dicer, which has endonuclease activity against DsRNA and pre- MiRNA s, cleaves a pre-miRNA stem-loop or a dsRNA, a 20-25 Base Pair double-stranded RNA fragment is formed with a 2 nucleotide 3' overhang at each end.12

  • One strand is integrated into the RISC complex. This strand is known as the guide strand and is selected by the Argonaute protein, the catalytically active RNase in the RISC complex, on the basis of the stability of the 5' end.Preall JB, He Z, Gorra JM, Sontheimer EJ. (2006). The single strand of RNA for which the 5' end is at the less stably base paired end of the double stranded siRNA is preferred for selection as the guide. Short interfering RNA strand selection is independent of dsRNA processing polarity during RNAi in Drosophila. ''Curr Biol'' 16(5):530-5.


  • The remaining strand, known as the anti-guide or passenger strand, is degraded as a RISC complex substrate.Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R. (2005). Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. ''Cell'' 123(4):631-40.



BINDING

The RISC complex with a bound siRNA recognizes .3


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