CHICAGO, Sept. 15 (Xinhua) -- Researchers at Northwestern University (NU) Medicine have identified how an RNA sequence called Evf2 regulates genes over an unprecedented distance in the genome, during a key process of embryonic brain development that affects adult seizure susceptibility and other neurological diseases.
In the study, the researchers described for the first time the complex process through which Evf2 affects the 3-D chromosomal structure, revealing how Evf2 directs a DNA element to four target genes over an unprecedented distance of 30 million bases.
The study demonstrated in a mouse model that the presence of Evf2 reduces seizure susceptibility; adult mice lacking Evf2 were susceptible to more frequent and more severe seizures, due to impaired GABA function.
"Understanding embryonic mechanisms of gene regulation that affect brain function in the adult can lead to the development of novel therapies for early intervention," explained Ivelisse Cajigas, research assistant professor of pediatrics at the university and first author of the study.
In addition, the researchers discovered that Evf2 regulates the expression of a serotonin receptor through repression of an enzyme called aldo-keto reductase in developing neurons.
"It's a novel pathway that allows for a whole new avenue of research into neuronal activity, and possibly mood disorder and seizure susceptibility treatment," said Jhumku Kohtz, research professor of pediatrics at NU.
Evf2, discovered by Kohtz's laboratory in 2006, is a long non-coding RNA that regulates transcription factors critical for the development of interneurons that produce GABA. Kohtz's team demonstrated that loss of Evf2 during early development results in GABA defects in adult mice, suggesting the significance of the non-coding RNA in neurological disorders.
The study has been published in Molecular Cell.
