Scientists discover how RNA regulates genes in embryo that affect seizure susceptibility

August 23, 2018

Scientists at the Stanley Manne Children's Research Institute at Ann & Robert H. Lurie Children's Hospital of Chicago and colleagues discovered how a type of RNA, called Evf2 enhancer RNA, regulates key genes during a critical stage in embryonic brain development. They found that by regulating these genes, the RNA plays an important role in cells that produce GABA neurotransmitters, which block impulses between nerve cells in the brain. Any disruption in this process could lead to seizures, mood disorders, schizophrenia, or other neurological disorders associated with GABA dysfunction. Their findings, published in Molecular Cell, ultimately could help identify therapeutic targets to prevent the development of neurological diseases.

"We provide evidence for RNA-dependent mechanisms that regulate the selection and expression of specific genes in GABAergic interneurons during embryonic brain development," says senior author Jhumku Kohtz, PhD, from Manne Research Institute at Lurie Children's and Professor of Pediatrics at Northwestern University Feinberg School of Medicine. "Clarifying what this RNA is doing expands our understanding of how certain neurological diseases develop, which brings us a step closer to intervening at the earliest stages."

Through a series of experiments, Dr. Kohtz and colleagues demonstrated that during embryonic brain development, the RNA selects and regulates four specific genes at unprecedented distances on the chromosome. By recruiting a protein that helps determine three-dimensional chromosomal architecture, the RNA correctly places a key DNA region near these specific genes, and allows them to be accessible for regulation. These genes are part of a network of genes that regulate the activity of nerve cells that make GABA, the major inhibitor in brain circuitry. Dr. Kohtz and colleagues showed in a mouse model that without this RNA, adult mice were more susceptible to seizures due to reduced GABA inhibitory function.

"We confirmed that Evf2 RNA decreases seizure susceptibility," says Dr. Kohtz. "It is exciting to discover how this RNA actually works in the embryo and the crucial impact it has on subsequent neurological activity in the adult brain."
-end-
This research was funded by the National Institute of Mental Health.

Research at Ann & Robert H. Lurie Children's Hospital of Chicago is conducted through the Stanley Manne Children's Research Institute. The Manne Research Institute is focused on improving child health, transforming pediatric medicine and ensuring healthier futures through the relentless pursuit of knowledge. Lurie Children's is ranked as one of the nation's top children's hospitals in the U.S.News & World Report. It is the pediatric training ground for Northwestern University Feinberg School of Medicine. Last year, the hospital served more than 208,000 children from 50 states and 58 countries.

Ann & Robert H. Lurie Children's Hospital of Chicago

Related Nerve Cells Articles from Brightsurf:

Nerve cells let others "listen in"
How many ''listeners'' a nerve cell has in the brain is strictly regulated.

Nerve cells with energy saving program
Thanks to a metabolic adjustment, the cells can remain functional despite damage to the mitochondria.

Why developing nerve cells can take a wrong turn
Loss of ubiquitin-conjugating enzyme leads to impediment in growth of nerve cells / Link found between cellular machineries of protein degradation and regulation of the epigenetic landscape in human embryonic stem cells

Unique fingerprint: What makes nerve cells unmistakable?
Protein variations that result from the process of alternative splicing control the identity and function of nerve cells in the brain.

Ragweed compounds could protect nerve cells from Alzheimer's
As spring arrives in the northern hemisphere, many people are cursing ragweed, a primary culprit in seasonal allergies.

Fooling nerve cells into acting normal
In a new study, scientists at the University of Missouri have discovered that a neuron's own electrical signal, or voltage, can indicate whether the neuron is functioning normally.

How nerve cells control misfolded proteins
Researchers have identified a protein complex that marks misfolded proteins, stops them from interacting with other proteins in the cell and directs them towards disposal.

The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.

Research confirms nerve cells made from skin cells are a valid lab model for studying disease
Researchers from the Salk Institute, along with collaborators at Stanford University and Baylor College of Medicine, have shown that cells from mice that have been induced to grow into nerve cells using a previously published method have molecular signatures matching neurons that developed naturally in the brain.

Bees can count with just four nerve cells in their brains
Bees can solve seemingly clever counting tasks with very small numbers of nerve cells in their brains, according to researchers at Queen Mary University of London.

Read More: Nerve Cells News and Nerve Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.