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2 genetic wrongs make a biochemical right
Date:10/20/2013

bly has several functions throughout the neuron but its main activity is to repress the translation of as many as 1,000 different mRNAs. By doing this, FMRP controls synaptic plasticity and higher brain function. Mice without the Fragile X gene, for instance, have a 15 to 20 percent overall elevation in neural protein production. It is thought that the inability to repress mRNA translation and the resulting increase in neural proteins may somehow hamper normal synaptic function in patients with Fragile X. But because FMRP binds so many mRNAs, and some proteins become more elevated than others, parsing which mRNA or combination of mRNAs is responsible for Fragile X pathology is a daunting task.

From Frog Egg to Fragile X

For years, Dr. Richter had been studying how translation, the process in which cellular ribosomes create proteins, went from dormant to active in frog eggs. He discovered the key gene controlling this process, the RNA binding protein CPEB. In 1998, Richter found the CPEB protein in the rodent brain where it played an important role in regulating how synapses talk to each other. At this point, his work began to move from exploring the role of CPEB in the developmental biology of the frog to how the CPEB protein impacted learning and memory. A serendipitous research symposium with colleagues at Cold Spring Harbor got him thinking about CPEB and Fragile X syndrome.

"Here I was, an outsider, a molecular biologist who had worked for years with frog eggs, in the same room with neurobiologists and neurologists, when they started talking about Fragile X syndrome and translational activity," said Richter. "It got me thinking that the CPEB protein might be a path to restoring the translational imbalance they were discussing."

Richter knew that CPEB stimulated translation and that FMRP repressed it. He also knew that animal models lacking the CPEB protein had memory deficits and that both proteins bound to many of the
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Contact: Jim Fessenden
james.fessenden@umassmed.edu
508-856-2000
University of Massachusetts Medical School
Source:Eurekalert

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