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. Author manuscript; available in PMC: 2009 Nov 1.
Published in final edited form as: Biochim Biophys Acta. 2008 Jul 22;1779(11):668–677. doi: 10.1016/j.bbagrm.2008.07.005

FIGURE 2. The R2D2/Dicer-2 heterodimer directs which siRNA strand is incorporated into RISC.

FIGURE 2

The R2D2/Dicer-2 heterodimer binds to siRNA duplexes and acts as a sensor of the thermodynamic stability of the siRNA ends. R2D2 binds to the more stable extremity whereas Dicer-2 binds more strongly to the less stable extremity. Unwinding of the duplex starts from the thermodynamic less stable extremity in a mechanism remaining mostly unknown. The strand having its 5’ terminus located at this end is loaded in the RISC and directs RNAi. The first step in the assembly of a cleavage-competent RISC occurs with the exchange of R2D2 for Ago2. Subsequently, other accessory proteins are incorporated and Dicer-2 dissociates from the complex.