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Science surprise: Toxic protein made in unusual way may explain brain disorder
Date:4/18/2013

ANN ARBOR, Mich. A bizarre twist on the usual way proteins are made may explain mysterious symptoms in the grandparents of some children with mental disabilities.

The discovery, made by a team of scientists at the University of Michigan Medical School, may lead to better treatments for older adults with a recently discovered genetic condition.

The condition, called Fragile X-associated Tremor Ataxia Syndrome (FXTAS), causes shakiness and balance problems and is often misdiagnosed as Parkinson's disease. The grandchildren of people with the disease have a separate disorder called Fragile X syndrome, caused by problems in the same gene. The new discovery may also help shine light on that disease, though indirectly.

In a new paper published in the journal Neuron, the U-M-led team presents evidence that a toxic protein they've named FMRpolyG contributes to the death of nerve cells in FXTAS and that this protein is made in a very unusual way.

Normally, DNA is transcribed into RNA, and then a part of the RNA is translated into a protein that performs its function in cells. Where this translation process starts on the RNA is usually determined by a specific sequence called a start codon.

The gene mutation that causes FXTAS is a repeated DNA sequence that is made into RNA but normally is not made into protein because it lacks a start codon. However, the investigators discovered that when this repeat expands, it can trigger protein production by a new mechanism known as RAN translation.

Corresponding author Peter Todd, M.D., Ph.D., notes that this unusual translation process appears to stem from a long chain of repeated DNA "letters" found in the genes of both grandparents and kids with Fragile X mutations. Todd is the Bucky and Patti Harris Professor in the U-M Department of Neurology

"Essentially, we've found that a sequence of DNA which shouldn't be made into protein is being made into
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Contact: Kara Gavin
kegavin@umich.edu
734-764-2220
University of Michigan Health System
Source:Eurekalert

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