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Fail-safe system may lead to cures for inherited disorders
Date:9/15/2011

Scientists at the University of California, San Diego School of Medicine have uncovered a previously unknown fail-safe (compensatory) pathway that potentially protects the brain and other organs from genetic and environmental threats. The discovery could provide new ways to diminish the negative consequences of genetic mutations and environmental toxins that cause neurological diseases and other maladies.

The findings are published in the Sept. 16 issue of the journal Molecular Cell.

Messenger ribonucleic acid (mRNA) is an essential molecule that "reads" genetic information contained within the human genome, and based on this information, generates proteins essential for life. A key inherent feature of mRNA is its "stop signal," which tells cellular machinery to stop reading the mRNA because it has produced a full-length protein. Importantly, in some aberrant mRNAs, the stop signal is displayed too early, resulting in the production of a shorter-than-normal protein. Some of these short proteins can be highly toxic to cells. To avoid their production, cells use a quality control pathway called nonsense-mediated mRNA decay or NMD, which rapidly degrades "bad" mRNAs with early stop signals.

In research published earlier this year, Miles Wilkinson, PhD, professor of reproductive medicine and a member of the UCSD Institute for Genomic Medicine, and colleagues, revealed that NMD is important for the normal development of the brain and the nervous system. Jozef Gecz, PhD, professor of pediatrics at the University of Adelaide, showed that when NMD doesn't work correctly, neurological conditions arise, ranging from mental retardation and attention-deficit disorder to schizophrenia and autism. These conditions are likely due to the production and accumulation of short proteins in the brain.

Like all components of the body, the NMD pathway is vulnerable to insults, such as environmental toxins or gene mutations. "If s
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Contact: Scott LaFee
slafee@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert

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