The circadian rhythm is your body’s own personal clock, a cycle of physical and mental processes that repeat roughly every 24 hours to manage your patterns of waking and sleeping. In the quest to understand what makes this “clock” tick, scientists have often looked at our so-called "clock genes", but a new study also suggests that part of the secret might lie in our “junk DNA".
The new study, published in the Proceedings of the National Academy of Sciences, has found that our circadian rhythm appears to be partially regulated by non-coding DNA sequences, components of an organism's DNA that do not encode protein sequences, better known as junk DNA.
"We've seen how the function of these clock genes are really important in many different diseases," Steve Kay, Provost Professor of neurology, biomedical engineering, and quantitative computational biology at the Keck School of Medicine, said in a statement.
"But what we were blind to was a whole different funky kind of genes network that also is important for circadian regulation and this is the whole crazy world of what we call non-coding microRNA."
A gene is a small section of DNA (or RNA) within the genome that contains a code for building proteins. However, the overwhelming majority of our DNA doesn’t actually code for any proteins — hence junk DNA. Despite its nickname, scientists have come to realize that non-coding DNA is far from useless trash. Formerly thought of as junk, previous work has shown that some non-coding chunks of microRNA, miRNAs, play an invaluable role in gene expression by preventing messenger RNA from making proteins. In effect, they regulate whether the gene is "on" and helping with the production of proteins or "off."
In this new study, researchers show how over 100 clusters of miRNAs have a profound effect on their cycles of sleep. The team used cells that had been engineered to glow on and off, based on the cell's 24-hour circadian clock cycle, like a light switch. Nearly 1,000 different miRNAs were then also introduced into each of the engineer cells. To see whether they had an effect on the circadian rhythm, the team inactivated certain particular miRNA and simply saw whether they “turned off” their glow.
"Much to our surprise, we discovered about 110 to 120 miRNAs that do this," said Kay.
Once the miRNAs were pinpointed, the team wanted to see whether tinkering with them would affect the behavior of mice. As they expected, switching off the miRNA changed the behavior of the mice when they were running around a toy wheel in a dark lab. They also noticed changes in the brain, retina, and lung tissue, likely related to shifts in their body's circadian rhythm.
The research isn’t just an interesting proof of concept, it could also pave the way for developments in biomedicine too, say the researchers. Perhaps surprisingly, a disturbed circadian rhyme is known to have some link to a handful of diseases, such as Alzheimer’s disease and other forms of dementia. By better understanding the genetic processes that underlie the cycle, the researchers hope it could open the door to new treatments.
“In the brain, we’re interested in connecting the clock to diseases like Alzheimer’s, in the lung we’re interested in connecting the clock to diseases like asthma,” explained Kay. “The next step I think for us is to model disease states in animals and in cells and look at how these microRNAs are functioning in those disease states.”
