Mechanisms of RNA Processing

A major goal of our research group is to understand how three dimensional structures determine 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 are critical in the development of various human diseases, including cancer. We recently published cryo-EM structures of the core Microprocessor complex, which initiates microRNA production using a network of RNA-protein interactions to detect primary microRNA transcripts.

Our overall approach involves combining 3D structure determination with in-depth biochemical dissection, using a broad array of techniques including 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 of Microprocessor

Stepwise assembly of proteins on the RNA substrate can be visualized via cryo-EM structures of the different stages .