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Linking Fragile X Syndrome proteins and RNA editing mistakes at nerve-muscle junction
Date:10/30/2011

PHILADELPHIA - The most common form of heritable cognitive impairment is Fragile X Syndrome, caused by mutation or malfunction of the FMR1 gene. Loss of FMR1 function is also the most common genetic cause of autism. Understanding how this gene works is vital to finding new treatments to help Fragile X patients and others.

Researchers from the Perelman School of Medicine at the University of Pennsylvania, and colleagues from Brown University, have identified the FMRP protein (encoded by FMR1) as a key player in RNA editing, a process in which the working copies made from DNA, called messenger RNAs, are chemically altered after being transcribed from the genome. Their findings were published online this week in Nature Neuroscience.

Since RNAs are used as the instructions to make proteins, mistakes in RNA editing at the neuromuscular junction (NMJ), the site at which motor neurons innervate muscle, may cause problems in nerve function. Previous work at Penn and several other institutions strongly suggested the role of FMRP to be in regulating the translation of certain types of RNA at the synapse, the space between two nerves, or between nerves and muscles.

"Most of the field has been focused on looking at FMRP interacting with specific RNAs and how it regulates their translation at the synapse," states lead author Thomas A. Jongens, PhD, associate professor of Genetics at Penn. "Here we've tapped into identifying a function that FMRP has in regulating another process called RNA editing that is important in regulating neural activity." In RNA editing, the information encoded by DNA into an RNA molecule is altered, thus affecting the functioning of the proteins encoded by that RNA.

"This work elegantly links the Drosophila FMR1 gene to both an RNA-editing pathway and the architecture of the neuromuscular junction synapse," says Donna Kransnewich, PhD, who oversees grants focused on mechanisms of human genetic dis
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

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Linking Fragile X Syndrome proteins and RNA editing mistakes at nerve-muscle junction
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