RNA interference (RNAi) has taken experimental biology by storm in recent years, since it has been greatly exploited as an ever increasingly effective tool to study gene function by gene silencing through RNAi. It is also being developed as a possible therapeutic tool. The RNAi machinery has been shown to have a role in development and appears to be important in maintaining stem cell identity. Though there has been remarkable progress in unraveling the components of the RNAi machinery, we are just beginning to understand how they work at the molecular level. The objective of this proposal is to provide the structural and biochemical framework, which will enable us to understand the mechanism of gene silencing by RNAi, with a focus on the signature component of the RNA-induced silencing complex (RISC), the Argonaute protein.
| Schalch, Thomas; Job, Godwin; Noffsinger, Victoria J et al. (2009) High-affinity binding of Chp1 chromodomain to K9 methylated histone H3 is required to establish centromeric heterochromatin. Mol Cell 34:36-46 |
| Tolia, Niraj H; Joshua-Tor, Leemor (2007) Slicer and the argonautes. Nat Chem Biol 3:36-43 |
| Faehnle, Christopher R; Joshua-Tor, Leemor (2007) Argonautes confront new small RNAs. Curr Opin Chem Biol 11:569-77 |
| Song, Ji-Joon; Joshua-Tor, Leemor (2006) Argonaute and RNA--getting into the groove. Curr Opin Struct Biol 16:5-11 |
| Joshua-Tor, L (2006) The Argonautes. Cold Spring Harb Symp Quant Biol 71:67-72 |
| Irvine, Danielle V; Zaratiegui, Mikel; Tolia, Niraj H et al. (2006) Argonaute slicing is required for heterochromatic silencing and spreading. Science 313:1134-7 |
