Role of non-coding RNA in inherited neurological and other brain disorders

A team of scientists, led by researchers at the University of California, San Diego School of Medicine, have uncovered a novel mechanism regulating gene expression and transcription linked to Spinocerebellar ataxia 7, an inherited neurological disorder.

Researchers have discovered that expression of the ataxin-7 gene – the cause of the neurological disorder spinocerebellar ataxia type 7 – has two regulators: a highly conserved, multi-tasking protein called CTCF and, surprisingly, an adjacent promoter containing non-coding RNA. Illustration courtesy of Christina Takamatsu-Butler, UC San Diego.

The discovery promises to have broad ramifications, suggesting that abundant non-coding transcripts of ribonucleic acid (RNA) may be key players in neurological development and function, and could be powerful targets for future clinical therapies.

The research, headed by Albert La Spada, MD, PhD, chief of the division of genetics in the UCSD department of pediatrics, and professor of cellular and molecular medicine, neurosciences and biological sciences, is published in the June 22 issue of the journal Neuron.

''Our paper highlights a number of important emerging themes in our understanding of gene regulation in the brain,'' said La Spada, who is also associate director of the UCSD Institute for Genomic Medicine.

''With the advent of new technologies, science has learned that the vast majority of our transcripts are non-coding,'' said La Spada. ''The challenge going forward is to determine what they do do, and if they have specific functions. It now seems increasingly likely that a multitude of these non-coding RNAs help finely tune transcription regulation in the brain, and perturbation of their work is linked to disease. If we can figure out exactly how, we should be able to gain new insights into how the brain is so precisely regulated – knowledge that may help us better understand how the brain works.'' 

Spinocerebellar ataxia 7 is one of several types of spinocerebellar ataxia (SCA), genetic degenerative disorders characterized by atrophy in the cerebellum of the brain, progressive loss of physical coordination – and in the case of type 7 – retinal degeneration that can result in blindness. There is currently no known cure.