Developing global insight into RNA regulation.

Systematic dissection of the activity of RNA-binding proteins (RBPs) has begun to yield global insight into how they work. The paradigm we have used has been the study of Nova, a neuron-specific RBP targeted in an autoimmune neurologic disorder associated with cancer. We have developed a combination of biochemical, genetic, and bioinformatic methods to generate a global understanding of Nova's role as a splicing regulator. Genome-wide identification and validation of Nova target RNAs have yielded unexpected insights into the protein's mechanism of action, its role in neurobiology, and the unique roles RBPs have in the biology of the neuronal synapse. These studies provide us with a paradigm for understanding the role of RBPs in neurons and in disease and, more generally, with the hope that it will be feasible to develop a comprehensive understanding of posttranscriptional regulation.

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