Minimal RISC (siRNA) pre-RISC (siRNA) Removal of siRNA passenger strand A short double-stranded RNA is passed from Dicer to an Argonaute and rendered single-stranded by removal and loss of the passenger strand. All Argonautes (AGO1, AGO2, AGO3, AGO4) can remove the passenger strand without cleaving it. AGO2 possesses endonucleolytic activity and cleaves the passenger strand of siRNAs, which facilitates but is not required for removal of the passenger strand (Matranga et al. 2005). <br>RNA helicase A is associated with the RISC loading complex can facilitate removal of the passenger strand.<br>The mechanism that selects which strand is retained as the guide RNA is not well understood in humans. Overhanging nucleotides and strength of base-pairing at each end of the input duplex are observed to influence strand selection.<br>Argonaute proteins directly or indirectly bind many other proteins and appear to be present in more than one distinct complex. Authored: May, B, 2012-02-05 Edited: May, B, 2012-02-05 Pubmed16271386 Pubmed17531811 Pubmed17932509 Pubmed18782830 Pubmed19401777 Pubmed19966796 Pubmed22106413 Reactome Database ID Release 432106615 Reactome, http://www.reactome.org ReactomeREACT_118852 Reviewed: Tomari, Y, 2012-02-10