Scientists have long known that cells don’t just follow DNA instructions blindly—they often make modifications to RNA, the molecule that carries genetic messages from DNA to the cell’s protein-making machinery. These edits can change the messages, sometimes leading to the production of different proteins than originally planned. One of the most common types of RNA editing is called adenine (A) to inosine (I) editing, where one building block in the RNA code is changed to another one. Inside cells, the inosine is then recognized by cellular protein production machinery as a guanosine (G), subtly altering the final protein made.

Although this RNA editing process has been studied for years, its role in the brain, especially in primates like monkeys and humans, has remained a mystery. That’s until now.

New detailed map of RNA editing in a mammalian brain

A new study led by Professor Yonglun Luo from the Department of Biomedicine and Steno Diabetes Center Aarhus, who is also an affiliated researcher at DANDRITE, has created the most detailed map to date of RNA editing across 38 different areas of the brain in the crab-eating macaque, a close relative of humans. The team discovered an astonishing 2.8 million RNA editing sites throughout the macaque brain.

Many of these editing sites appeared in genes involved in synaptic signaling and the production of neurotransmitters—the process by which nerve cells communicate with each other. This suggests that the RNA editing might play a key role in controlling how neurons talk to one another, potentially influencing how the brain processes information.

“Finding these RNA editing sites that are preserved through evolution challenges how we think about the proteins we study. If we only look at the protein sequences directly predicted from the reference genome and ignore these RNA edits, we might not be seeing the real proteins working inside living cells,” explains Professor Yonglun Luo.

Editing is linked to neuron density and brain function

Interestingly, the researchers noticed that brain regions with more neurons had higher levels of RNA editing events. This could mean that as brain areas become more complex, they rely more on RNA editing to regulate their functions.

The study also found the most intense RNA editing activity in parts of the brain responsible for complex tasks like thinking, feeling, and moving. Many of the edits were found in genes linked to neurotransmission and the brain’s ability to learn and remember.

Comparing their results with data from mice, pigs, and humans, the researchers discovered that primates—macaques and humans—share a surprisingly large number of RNA editing sites, especially in genes important for neuron communication. Nearly 500,000 editing sites were common between macaques and humans, many linked to memory and learning.

“These findings highlight the critical role RNA editing plays in the primate brain and suggest it may be key to the advanced cognitive abilities seen in humans and other primates. The conservation of these editing sites over millions of years of evolution also indicates that disruptions in RNA editing could contribute to brain disorders such as autism, schizophrenia, and Alzheimer’s disease,” Yonglun explains.

The study was conducted in collaboration with Associate Professor Jacob B. Hansen from the Department of Biology, University of Copenhagen, and was recently published in Nucleic Acids Research.  

Behind the study:

• For more information, contact: Yonglun Luo, alun@biomed.au.dk
   
• Basic research
   
• Collaborators: Department of Biology, University of Copenhagen
   
• External funding: Lundbeck Foundation, Novo Nordisk Foundation
   
• No impartiality issues
   
• Peer-reviewed article
   
• Direct link to the abstract or the scientific article:  
  https://academic.oup.com/nar/article-abstract/doi/10.1093/nar/gkaf534/8166790 utm_source=advanceaccess&utm_campaign=nar&utm_medium=email