Dark genome is involved in Rett syndrome
Today, there is not any effective treatment for the disease beyond the control of its symptoms. Rett syndrome is usually due to the presence of a mutation in Mecp2, an epigenetic gene that, as a magnet, regulates the expression of many other cell genes.
Esteller's research group works with a mouse model which faithfully reproduces the characteristics of human Rett syndrome. In the study, researchers compared the expression of long chains of RNA in healthy and diseased animals and found that the presence of mutations in Mecp2 gene causes alterations on the activity of long non-coding RNA (lncRNA), molecules which are part of the so-called dark genome. The function of dark genome, which represents 95 % of human genome, is still unknown.
One of these altered lncRNAs regulates the function of a key neurotransmitter in the nervous system in all vertebratesʼ brain, the GABA receptor. "Its alteration may explain the impairment of communication between neurons in girls affected by Rett syndrome", states Esteller. “Besides increasing the knowledge about diseaseʼs causes, this finding could open the door to new therapeutic strategies that target lncRNA molecules or GABA receptor”, adds the researcher.
The study was supported by the Department of Health of the Government of Catalonia, the Catalan Institution for Research and Advanced Studies (ICREA), the Spanish Health Ministry, the European projects DISCHROM and EPINORC, Jérôme Lejeune Foundation, and the Catalan Association Rett Syndrome.
Petazzi, P.; Sandoval, J.; Szczesna, K.; Jorge, O. C.; Roa, L.; Sayols, S.; Gómez, A.; Huertas, D., and Esteller, M. "Dysregulation of the long non-coding RNA transcriptome in a Rett syndrome mouse model". RNA Biology, April 2013, 10(7).