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Molecular basis of mental retardation uncovered

ately 1 in 2,000 males and 1 in 4,000 females worldwide. Symptoms include mild to moderate cognitive and behavioral deficits as well as subtle facial malformations. In addition, the brain cells, or neurons, of people with the disease have abnormal physical features: their "dendritic spines" - the finger-like projections on the ends of neurons that are required for communication with other neurons - are unusually long and spindly.

The disease originates when genetic mutations in the FMRP gene, which lies on the X chromosome, cause FMRP not to be produced. But unlike the well-studied Down syndrome, which occurs when a portion of a chromosome is duplicated in the womb, much remains unclear about the molecular basis of fragile X syndrome.

"The problem of fragile X is intriguing, because the loss of a single protein causes a variety of behavioral and physical changes," says Jennifer Darnell, Ph.D., lead author of one of the Cell reports and a research assistant professor at Rockefeller. "Before this, the consequences of losing the fragile X mental retardation protein on other brain proteins was unknown."

Previously, it was known that FMRP, first identified a decade ago, binds to messenger RNA (mRNA) molecules - which carry genetic information (DNA) from a body cell's nucleus to its protein-making machinery - yet the specific mRNAs involved as well as the overall purpose of this protein remained elusive.

Now, the researchers present several important clues, which together suggest that FMRP may turn up or down the production of certain brain proteins by binding to their mRNA molecules, and thus influencing the cell's protein-making machinery. This type of protein regulation is a crucial aspect of every cell's life, and in the case of brain cells, is essential for learning and memory formation. A key feature of the current work is the identification of the specific mRNAs that FMRP binds to, as
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Contact: Whitney Clavin
clavinw@rockefeller.edu
212-327-7900
Rockefeller University
15-Nov-2001


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