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NIH: Mental Health Protein Foun In Mice and Flies; Separate study Finds Possible Human Link

The protein topoisomerase is considered the "magician of the DNA world." It stabilizes DNA's double helix structure during replication and repair, enabling DNA to unwind and then rewind without breaking.

Topoisomerase, was thought not to have a role in RNA—a single stranded genetic structure. In an important new study, however, researchers at the National Institute on Aging at NIH have discovered the first RNA topoisomerase, Top3β, in animal cells and determined it to be crucial for normal neurodevelopment in mice and fruit flies. Specifically, the scientists found Top3β genetically interacts with protein FMRP (fragile X mental retardation protein) to promote healthy brain function and protect against mental disorders.

Furthermore, they report that some mutations in FMRP that cause Fragile X syndrome, the leading cause of autism and strongly associated with schizophrenia in humans, also disrupt the interaction between FMRP and Top3β. These findings are reported in the August 4, 2013, online issue of Nature Neuroscience.

In the same issue of Nature Neuroscience is a paper linking Top3β deletion in a Finnish population to schizophrenia and/or intellectual disability. This suggests a likely human application for the companion finding in animal models. Researchers propose that these new reports might point the way to targets for future therapy for patients with these mental disorders.


Xu D., et al. Top3β is an RNA topoisomerase that works with fragile X syndrome protein to promote synapse formation. Nature Neuroscience. Published online August 4, 2013; DOI: 10.1038/nn.3479

NIH:; National Institute on Aging

August 5, 2013

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