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Technique may identify novel disease genes at a faster clip

Researchers have used ultraviolet light to "weld" a key regulatory protein to its RNA targets, creating a new tool that can be used to identify novel proteins involved in a variety of human diseases.

Using this technique, the researchers have identified an array of RNA molecules regulated by the RNA-binding protein, Nova, which has been implicated in an autoimmune neurodegenerative disease. The researchers believe their technique may help in finding the RNA targets of other proteins involved in neurological diseases, including the most prevalent form of mental retardation, the Fragile X syndrome.

Robert B. Darnell, a Howard Hughes Medical Institute investigator at The Rockefeller University, led the research team that reported its findings in the November 14, 2003, issue of the journal Science.

Darnell and his colleagues have been investigating the function of Nova, an RNA-binding protein that regulates alternative splicing. In alternative splicing, messenger RNA, carrying the blueprint for a protein from the cell's genes, is processed in such a way that it can produce a number of slightly different proteins. Apart from its role in alternative splicing, the Nova protein is of great interest, said Darnell, because it is targeted by the immune system in the neurodegenerative disease, paraneoplastic opsoclonus myoclonus ataxia, which causes progressive loss of motor control.

"Previous work in our laboratory had revealed how Nova bound to RNA, and we had identified a couple of specific target RNAs in the brain," said Darnell. "These studies led us to discover that Nova was the first mammalian splicing factor that was restricted to a particular tissue. We then really wanted to know what is the full array of RNAs that Nova binds to and regulates in the brain?"

According to Darnell, Nova is just one of a rapidly growing list of RNA-binding proteins that are be
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
13-Nov-2003


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