2 min readLocked RNA Editing Yields Odd Fly Behaviour

Instructions for the protein-making machinery of cells Yiannis Savva and other members of the research team found that highly edited fruit flies had strikingly different behaviors compared to controls. Image: Mike Cohea/Brown University

Providence, RI ― Because a function of RNA is to be translated as the genetic instructions for the protein-making machinery of cells, RNA editing is the body’s way of fine-tuning the proteins it produces, allowing us to adapt. The enzyme ADAR, which does this editing job in the nervous system of creatures ranging from mice to men, even edits itself.

In a new study that examined the self-editing process and locked it down at two extremes in fruit flies, Brown University scientists found some surprising insights into how this “fine-tuning of the fine-tuner” happens, including bizarre behavioural effects that come about when the self-editor can’t edit.


The speed of courtship may seem like a triviality, but not when a creature’s most important function in the wild is to reproduce successfully, said biologist Robert Reenan, senior author of the study, which appears in the April 24 edition of Nature Communications.

“The females in nature may not like a male that has less interest in sex,” Reenan said. “That’s not going to be very adaptive.”

Reenan, first authors Yiannis Savva and James Jepson, and the rest of the team observed other peculiar behaviours too. Stuck in a vial, as research flies often are, the highly self-edited ones would tend to congregate near the well-lit top, while the unedited ones would mill about at the bottom where the food was. Only the controls would consistently move about the whole vial.


All of the strange behaviours provide evidence for the idea that the self-editing process can have significant effects on behaviour in a living animal, Reenan said. “We’re showing this is like an adjustment knob for some behaviors.”

The inner workings

In more fundamental experiments, Reenan’s team observed that self-editing varied neuron by neuron. They also found that the more self-editing occurs in a fly’s dADAR, the less RNA editing activity there is in a neuron. They even identified a mechanism for this, which is that more highly edited dADAR ends up becoming sequestered in a pocket of the nucleus ― a phenomenon they saw under the microscope after tagging dADAR to fluoresce. Flies with less RNA editing activity still had levels of dADAR that were comparable to those of other flies. They were just editing their dADAR more and keeping it in a kind of nucleus dry dock.


“Auto-editing changes with temperature,” Reenan said. “Out there in the wild, the same fly, at two different temperatures is going to express a different set of proteins in its brain.”

One of the next questions Reenan said he’d like to ask is what other external, or “abiotic” factors, such as diet, might also lead to a fundamental change in dADAR self-editing levels. Given that some human mental illnesses, epilepsy, suicidal depression, and ALS (Lou Gehrig’s Disease) have been associated with errant ADAR activity, it may help advance potential therapies to know how auto-editing could be modulated in behaving organisms.


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