RNA dysregulation in autism

  • Awarded: 2012
  • Award Type: Research
  • Award #: 240432

Growing evidence links errors in genetic control to autism. However, an emerging theme in the pathobiology of human neurologic disorders is that such errors are often found in the regulation of RNA rather than DNA. This fascinating set of observations suggests that whole-genome analysis may be complemented by new technologies that can be used to study RNA regulation. Robert Darnell and his colleagues at The Rockefeller University in New York plan to do just that.

The most common single-gene cause of autism is the same genetic mutation that causes fragile X syndrome. The mutation, in the FMR1 gene, results in the loss of the RNA-binding protein FMRP. FMRP inhibits translation of messenger RNA into many gene products that are linked to autism. Similarly, errors in RNA processing have been linked to the dysfunction of neuronal splicing factors such as RBFOX1 and NOVA.

Darnell anticipates that not all defects in RNA transcript regulation will be detectable by current gene expression analyses. These defects may be more directly identified through binding maps of relevant RNA-binding proteins. His team plans to use a breakthrough technology that is able to pinpoint sites of RNA regulation in whole tissues such as the brain, and use it to study RNA control by FMRP, RBFOX1 and NOVA in autism brain samples.

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