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.

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RELEVANT PUBLICATIONS

• Structural basis for RNA slicing by a plant Argonaute. NSMB 2023

• A tiny loop in the Argonaute PIWI domain tunes small RNA seed strength. EMBO Rep. 2023

• Relaxed targeting rules help PIWI proteins silence transposons. Nature 2023

• The molecular mechanism of microRNA duplex selectivity of Arabidopsis ARGONAUTE10. NAR 2022

• A structured RNA motif locks Argonaute2:miR-122 onto the 5' end of the HCV genome. Nature Communications. 2021

• Structural basis for piRNA targeting. Nature. 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

• Structural basis for microRNA targeting. Science. 2014

• Highly complementary target RNAs promote release of guide RNAs from human Argonaute2. Mol Cell. 2013

• The crystal structure of human Argonaute2. Science. 2012

• The molecular architecture of human Dicer. Nat Struct Mol Biol. 2012

• Structure of the human Dicer-TRBP complex by electron microscopy. Structure. 2009