Identifying RNA-protein interactions important in neuronal function

Jennifer Darnell, Kate Dredge, Kirk Jensen and Robert B. Darnell
Laboratory of Moloecular Neuro-Oncology, The Rockefeller University, New York, NY

The brain appear to harbor a unique set of proteins that regulate neuron-specific RNA metabolism. Several sets of these proteins have been identified as target antigens in autoimmune neurologic diseases triggered by systemic malignancies. We have taken a multistep approach to identify the function of these neuronal RNA binding proteins. Several complimentary approaches have been undertaken to identify the array of RNAs to which these proteins bind. For example, RNA selection has been used to identify complex RNA targets for the Nova RNA binding protein, and for the related fragile-X mental retardation protein, FMRP. These targets have successfully been used to screen databases of RNAs and identify candidate in vivo RNA targets. We have combined biochemical assays with functional assays, relying on genetically null animals to confirm the relevance of these sets of RNAs.