Little-Studied RNA Might be Key to Regulating Genetic Disorders Like Epilepsy, Autism
November 13, 2024
Article Published by Northwestern Feinberg School of Medicine
Featuring the work of CURE Epilepsy grantee Dr. Gemma Carvill
When a gene produces too much protein, it can have devastating consequences on brain development and function. Patients with an overproduction of protein from the chromodomain helicase DNA binding (CHD2) gene can develop a rare and severe neurodevelopmental disorder causing them to become non-ambulatory, nonverbal and with profound intellectual delays. In a new study, scientists at Northwestern Medicine and the Broad Institute of MIT and Harvard have discovered that a characteristic of patients with this rare disorder is an absence of a long non-coding RNA called CHASERR (CHD2 adjacent, suppressive regulatory RNA). RNA stands for “ribonucleic acid,” which is found in all living cells and plays a crucial role in protein synthesis. In patients with this rare disorder, CHASERR is deleted and CHD2 protein production goes into overdrive. Long non-coding RNAs exist in the so-called “Wild West,” or the 99 percent of the human genome that is currently understudied. “There are thousands of long non-coding RNAs, but, until this study, we didn’t know what they did,” said Gemma Carvill, PhD, the study’s corresponding author. The study specifically focused on the CHD2 gene, which causes autism and epilepsy. Carvill said future studies that attempt to manipulate CHASERR might have success in controlling the amount of CHD2 protein that is produced, thereby leading to more effective treatments for patients. Today, when someone undergoes genetic testing to identify variants or changes that might be linked to genetic disorders or diseases, they first receive gene panels or exome sequencing — which focuses on only 1 percent of the human genome that codes for proteins. “It is mind-boggling that we only know what 1 percent of the human genome does, and we have very little idea what the other 99 percent does,” Carvill said. “We ignore it, and our study highlights why we shouldn’t.”