Mechanisms of RNA Processing

A major goal of our research group is to understand how structures dictate the mechanisms of RNA-mediated gene-regulation. Only about 2% of the transcribed genome is estimated to be coding for protein. How do the rest, known as noncoding RNAs (ncRNAs), work? How are ncRNAs recognized and what do they recognize? How do structural elements contribute to the activity of ncRNAs? 

We are particularly interested in a family of ncRNAs called microRNAs. MicroRNAs modulate messenger RNA translation and play key roles in development and diseases including cancer. We determined cryo-EM structures of the core Microprocessor complex--the processing enzyme to initiate functional microRNA production. In addition to the core mechanisms of RNA recognition and cleavage, we are also investigating regulatory mechanisms that help tune microRNA biogenesis.  

Our overall approach involves combining 3D structure determination with in-depth biochemical dissection, using a broad array of techniques including chemical probing, X-ray crystallography, cryo-electron microscopy, NMR spectroscopy, molecular biology, enzymology, next-generation sequencing, and eukaryotic cell-based assays.

We revealed structural details of how the human Drosha/DGCR8 complex recognizes primary microRNAs (Partin et al. 2020).

Biophysical and Biochemical Characterization of Microprocessor-RNA complexes

Cryo-EM structures reveal stepwise assembly of the Microprocessor-RNA complex