Protein and RNA Structure
A major strength of the lab is the investigation of biology through molecular form and function. We determine structures of RNA-protein complexes using x-ray crystallography and electron microscopy and combine these results with biochemical and cellular assays that probe molecular mechanisms. Most of our efforts in recent years have been devoted to understanding how Argonaute and Piwi proteins use small RNAs to establish their extraordinary gene-silencing properties.
A structured RNA motif locks Argonaute2:miR-122 onto the 5' end of the HCV genome. Nature Communications. 2021
mRNA structural dynamics shape Argonaute-target interactions. NSMB. 2020
Robust differential microRNA targeting driven by supplementary interactions in vitro. RNA. 2020
Structural Basis for Target-Directed MicroRNA Degradation. Mol Cell. 2019
Beyond the seed: structural basis for supplementary microRNA targeting by human Argonaute2. EMBO J.
Helix-7 in Argonaute2 shapes the microRNA seed region for rapid target recognition. EMBO J. 2018
A Dynamic Search Process Underlies MicroRNA Targeting. Cell. 2015
Water-mediated recognition of t1-adenosine anchors Argonaute2 to microRNA targets. eLife 2015
Highly complementary target RNAs promote release of guide RNAs from human Argonaute2. Mol Cell. 2013
The molecular architecture of human Dicer. Nat Struct Mol Biol. 2012
Structure of the human Dicer-TRBP complex by electron microscopy. Structure. 2009