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Understanding key protein in Fragile X syndrome

December 1, 1999 Fragile X syndrome, the most common inherited form of mental retardation, results from a mutation that somehow affects how genetic messages travel from the cell's nucleus to its protein manufacturing apparatus. With the identification of three key molecular actors in that ferrying process, researchers are now bearing in on the cellular mechanisms underlying Fragile X syndrome, and perhaps other causes of mental retardation as well.

For a condition with such a delicate-sounding name, Fragile X syndrome can have powerful effects, ranging from learning disability and hyperactivity to severe mental retardation. Mutations in a gene known as FMR1 produce the disorder, and Stephen Warren, a Howard Hughes Medical Institute (HHMI) investigator at Emory University, has been studying this gene and its corresponding protein, called FMRP, since he and his colleagues first identified them in 1991.

"When we first identified FMRP, it didn't look like any other protein that had been previously identified, so we really didn't know what it did. But by slowly chipping away over the years, we and others have learned a lot about it," said Warren.

For example, Warren's group has determined that FMRP binds to messenger RNA molecules, forming a complex called RNP (ribonucleoprotein particle). They also know that FMRP shuttles between the cell's nucleus and cytoplasm, and that it visits ribosomes, where the genetic code for building proteins is translated. From all this evidence, they speculated that FMRP must somehow be involved in the translation process.

To understand more about FMRP's function in the cell, Warren's group needed to identify the protein's partners in the RNP complex, a feat that had defied conventional protein-purifying techniques. Not to be thwarted, the researchers developed a set of antibodies that allowed them to isolate not only FMRP, but also messenger RNA (mRNA) and at least six other proteins from the complex. Warren, togeth
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Contact: Joseph Alper
alperj@hhmi.org
720-890-1956
Howard Hughes Medical Institute
29-Nov-1999


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