A Research Blog

New study discovers pervasive RNA changes in the epileptic brain

Epilepsy is the fourth most common neurological disorder afflicting over 60 million people worldwide. The disorder is characterised by a tendency to have recurring, unprovoked seizures, and can cause other health problems. While seizures can be in part controlled by medication, there is currently no effective cure for epilepsy.  More fundamental research is needed to better understand the disorder and to identify treatment targets.

DNA is a molecule that carries the genetic instructions used in the growth and function of all living organisms, while RNA is a molecule that, amongst other functions, is essential for the transmission and use of these genetic instructions. Both DNA and RNA are essential for all known forms of life.

Currently, most of the research in epilepsy is focused on mutations and variations in the DNA. However, other types of variations might occur specifically in the RNA, which is a process called RNA  editing. Hence, it may be important to examine both DNA and RNA variations in epilepsy. This new research shifts the focus from solely analysing DNA, to analysing RNA editing in the epileptic brain.

In a study published in Genome Research, Duke-NUS Medical School’s (Duke-NUS) Associate Professor Enrico Petretto examined the role of RNA editing in the brain and discovered a new disease mechanism for epilepsy. The study’s findings breathe new life into the field of RNA editing research and therapy development for epilepsy.

In the largest study of RNA editing in the brain to date, Assoc Prof Petretto’s team used data from 200 mouse hippocampi (from 100 epileptic mice vs 100 healthy mice) and identified a replicable set of 256 RNA sites that showed variable levels of editing (i.e., changes occurring specifically in the RNA sequence) between epileptic and healthy mice. These RNA edited sites overlapped with 87 genes, highly relevant to the basic biological processes occurring in epilepsy. Additionally, the increased RNA editing level in the epileptic mouse hippocampus was quantitatively associated with the occurrence and the frequency of seizures – the more RNA editing that was observed, the more seizures that were observed.

The team showed that the set of genes with differential RNA editing informed specific biological processes occurring in the brain, which present new mechanisms that can trigger epilepsy and can potentially be targeted to develop new therapies.

The findings are exciting from a therapeutic standpoint because they suggest new avenues to think about when treating epilepsy. They also suggest that researchers more fully consider the somewhat overlooked biological function of RNA editing and its, equally important, fundamental contribution to disease. The study shows, for the first time, that RNA editing is significantly and reliably associated with the occurrence of epilepsy. As a field of research, RNA editing has gone through intense scrutiny in the past, but this new comprehensive study argues that it is worth examining this biological process in brain research.

Authors include Dr Sarah Langley from Duke-NUS and co-senior author Professor Michael Johnson from Imperial College London. This research was supported with funding from the European Union’s Seventh Framework Programme (FP7/2007-2013) and UCB Pharma (E.P., M.J.) and the Duke-NUS Signature Research Programme, with funding from the Singapore Ministry of Health to E.P.


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