Hidden gene could help control anxiety


Proposed working model depicting activity-dependent regulation of Gomafu lncRNA in the mouse prefrontal cortex.

A new study has found the mechanism used by a hidden gene to affect how the brain responds to stressful experiences, in a discovery that could eventually help control anxiety.

University of Queensland scientists, together with colleagues at the University of California Irvine and the Garvan Institute of Medical Research, discovered that Gomafu, a gene recently associated with schizophrenia, causes behaviours that may be key to understanding both schizophrenia and anxiety.

UQ Queensland Brain Institute researcher Dr Timothy Bredy said by looking across the entire genome for genes responsive to fear-related experience, they found that Gomafu was regulated in the adult brain.

“When Gomafu is decreased or turned off, we observe the kind of behavioural changes that are seen in anxiety and schizophrenia,” Dr Bredy said.

The gene, identified as a long non-coding RNA, was found to occur within a section of the genome most commonly associated with “junk” DNA – the 98 per cent of the human genome that, until recently, was thought to have no function.

“Early biologists thought that DNA sequences that do not make protein were remnants of our evolutionary history, but the fact is that these sequences are actually highly dynamic and exert a profound influence on us,” Dr Bredy said.

“We found that non-coding genes such as Gomafu may represent a potent surveillance system that has evolved so that the brain can rapidly respond to changes in the environment.

“A disruption of this network in the brain might contribute to the development of neuropsychiatric disorders.”

These findings will help to resolve the current criticisms surrounding genome-wide association studies, where the majority of gene mutations related to neuropsychiatric disorders are found within non-coding sequences of DNA that were thought to have no biological impact.

QBI PhD candidate Ms Paola Spadaro said RNA-directed regulation of these processes had emerged as an important feature of human development, but this was the first time long non-coding RNA activity had been detected in the brain in response to experience.

This finding will enable better prediction of vulnerability and resilience to developing a neuropsychiatric disease, with the primary goal to develop better treatment approaches across the lifespan.

  • Spadaro PA et al. (2015) Long noncoding RNA-directed epigenetic regulation of gene expression is associated with anxiety-like behavior in mice. Biological Psychiatry [Epub ahead of print]. [abstract]

Source – The University of Queensland

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