Researchers describe new technique for cataloging RNA targets in rare brain disease

RNA, often thought of as merely the chemical messenger that helps decode DNA's genetic instructions for making proteins, can itself play a crucial role in regulating protein expression. Not surprisingly, this regulation occurs through proteins that bind to RNA. All cells in the body, especially nerve cells in the brain, use and regulate RNA in an exquisite fashion.

Scientists have previously shown that defects in RNA binding underlie several human brain disorders, but their RNA targets have been a mystery. Researchers at Rockefeller University have now developed a method that allows scientists, for the first time, to develop complete lists of RNAs that are regulated by RNA binding proteins.

According to the researchers, the method will generally be useful for scientists studying other diseases that result from defects in RNA regulation, including several autoimmune diseases, spinal muscular atrophy, and Fragile X mental retardation.

Reporting in the Nov. 14 issue of the journal Science, a team of scientists led by Robert B. Darnell, M.D., Ph.D., a professor at Rockefeller and an investigator at the Howard Hughes Medical Institute, showed that their new technique, called CLIP, can rapidly identify all the RNAs that bind to a protein that has been linked to the brain disorder POMA, or paraneoplastic opsoclonus myoclonus ataxia. These experiments were able to show that a protein called Nova plays a critical role in regulating alternative splicing within the brain.

"We have developed and validated a new methodology we term CLIP to help scientists interested in the role of RNA binding proteins in biology and disease," says Darnell. "We used CLIP to show that an RNA-binding protein called Nova regulates a biologically coherent -- that is, not a random -- set of RNAs whose proteins function at the synapse of nerve cells in the brain. This finding may help us better understand and treat the variety of diseases that involve the misregulation o

Contact: Joseph Bonner
Rockefeller University

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