This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. RNA interference (RNAi) is a conserved mechanism of eukaryotic gene silencing and regulation. In humans RNAi and the related micro-RNA pathways are carried out by a family of large, related protein complexes, generically termed RNA induced silencing complexes (RISCs). The goal of this work is to determine molecular structures of the various forms of RISC in an effort to better understand the mechanism of gene silencing by RNAi.