Research Topics

Neurobiology, Protein-Nucleic Acid Interactions, Regulation of Gene Expression

Disease Research Interests

Neurological and Behavioral Disorders

B.S., University of Wisconsin-Madison (Bacteriology)
Ph.D., University of Wisconsin-Madison (Genetics)
Postdoctoral fellow, University of Chicago
Postdoctoral fellow, Emory University

Molecular basis of disease, post-translational modifications, regulation of RNA expression, RNA-protein interactions

The human brain is made up of billions of specialized cells called neurons that act together to drive behavior, learning and memory through incompletely defined mechanisms. Neurons communicate with each other through their long cellular extensions that are composed of proteins. Proteins are encoded by messenger RNAs (mRNAs), which are copies of genes encoded by the hereditary material DNA. mRNAs are the recipes for proteins that are made in the cell and give the cell its unique identity. The subject of our current research is a recently characterized protein, RNA helicase MOV10, which is a cofactor of the microRNA pathway protein AGO2 and also of the Fragile X protein FMRP. We demonstrated that MOV10 is necessary for early embryonic development across species and for normal neuron development that includes producing the branches that connect neurons. The goals of our work are to identify the mRNAs that MOV10 unwinds, to understand how MOV10’s unwinding activity is regulated by modification and/or associated proteins and to determine how MOV10 participates in the production of the dendritic branching that is critical for neuronal function.

Bursts of protein translation are required for normal development and neuronal function but it is unknown how this process is regulated. The goal of our research is to explore the key role of RNA unwinding on RNA fate. The RNA helicase MOV10 binds in proximity to MicroRNA Recognition Elements (MREs) in 3’UTRs.  It unwinds secondary structures in the RNA to allow access of the primary effector protein of the miRNA pathway, AGO2, to MREs. Using individual nucleotide Crosslinking Immunoprecipitation (iCLIP), we showed that MOV10 binds mRNAs encoding neuronal projection and cytoskeletal proteins in developing mouse brain, suggesting a role for MOV10 in regulating translation in dendrites. The hypothesis being tested is that MOV10 binds RNA G-quadruplexes (GQs), which are stable RNA secondary structures, to modulate AGO2 association to MREs in the 3’UTR. We have created a number of engineered mouse lines that allow us to explore MOV10’s role in brain development and behavior.

Dept. of Cell and Developmental Biology
University of Illinois
B107 CLSL
601 S. Goodwin Avenue
Urbana, IL 61801