RNA editing plays a critical role in fruit flies’ sense of smell and social interactions

Think of your DNA as a set of instructions or a recipe book that tells your body how to make everything it needs to function, from proteins to cells. Every time the body needs to make something, it reads those instructions. But sometimes, the body can make small changes to those instructions. That’s where RNA editing comes in.

RNA editing is like a proofreading process that happens after your DNA instructions have been copied. Instead of simply following the recipe exactly, your cells can make tiny changes to the instructions. These changes can help the body adapt to different situations by creating new versions of proteins that might be better suited to certain tasks.

In both humans and fruit flies, RNA editing prevents autoimmune responses and adjusts protein functions. However, in humans, most edits occur in noncoding regions, and only a small fraction result in changes in protein function. In contrast, in flies, the majority of RNA editing events occur in sequences that directly produce proteins.

Given the abundance of RNA editing events that lead to changes in protein coding sequences in flies, a major challenge is to determine which of these thousands of events are biologically important and worthy of study.

Researchers from Bar-Ilan University in Israel have identified such a phenomenon and determined its essential role in the sense of smell and social interactions of fruit flies. The results of their study are published in the journal Scientific progress.

To select the particular editing event to study, the research team focused on editing events that have been evolutionarily conserved for millions of years in several fruit fly species. They narrowed their search to a specific event in the GluClα channel that may have significant functional importance. This event, in which isoleucine is changed to valine, is crucial to the flies’ ability to detect odors for social interactions that depend on the detection of pheromones, small molecules that enable communication between individuals.

To test the importance of this site, the researchers used CRISPR technology to remove the RNA editing. They then conducted a battery of behavioral tests that repeatedly and clearly revealed that flies whose RNA had not been edited had difficulty smelling and communicating socially. Flies whose GluClα channel had no alterations had a reduced ability to be attracted to the smells of apple juice or alcohol and to avoid odors that alerted them to danger. They also had a reduced ability to interact socially, which is necessary for survival and reproduction.

Further analysis identified specific neurons in the brain responsible for processing odors that were affected by the lack of RNA editing. The researchers proposed a model to explain how editing at different locations on the GluClα channel contributes to its proper function, and why the editing is necessary rather than just a constant mutation.

“Our results highlight how essential RNA editing is for normal behavior,” said Professor Galit Shohat-Ophir, of Bar-Ilan University’s Goodman School of Life Sciences, Gonda Brain Research Center and Institute of Nanotechnology.

“We were surprised to see how large and consistent an impact the absence of modification had on the flies. This underscores how critical these tiny changes are to the expression of complex behaviors,” added Prof. Shohat-Ophir, who led the study with graduate student Hila Zak, in collaboration with Prof. Moshe Parnas of Tel Aviv University, Prof. Jun Billy Li of Stanford University, and Dr. Yoav Pass of Bar-Ilan University.

This study highlights the enormous potential and importance of RNA editing in animal physiology and behavior. In future research, Professor Shohat-Ophir hopes to uncover how the level of editing is regulated to allow flexibility to respond to environmental changes and internal needs.