If you turn the volume low enough, you cannot hear the radio. New research has found that circadian rhythm strength has a “volume control” as well: the protein REV-ERBα.

Most research on the circadian rhythm deals with what happens, when and why. However, the strength of a molecular signal is also important. If a signal is too weak, it will not have any effect. If it is too strong, it could interfere with other functions. In molecular biology as in Goldilocks, only “just right” will do. Researchers have discovered that a protein called REV-ERBα, already known to be important in the circadian rhythm, may be the factor that controls circadian rhythm strength, keeping it in the amplitude range where it is most effective.

What Is REV-ERBα?

Like many proteins in the human body, REV-ERBα appears to play a variety of roles. It is an integral part of thyroid hormone receptors, important in regulating the metabolism of cartilage and also plays a large role in the circadian rhythm. Its role in the circadian rhythm has been a subject of much research because of this protein’s unusual method of action. During the time of day when certain circadian genes should not be expressed, REV-ERBα binds to the DNA for these genes to physically stop transcription.

The “Volume” Control of Circadian Rhythm Strength

Like many proteins related to the circadian rhythm, REV-ERBα is expressed in a rhythmic fashion. It is highest during the day and reaches its lowest levels at night. Researchers decided to turn off the enzyme that degrades REV-ERBα, keeping its levels high at night. The timing of the circadian rhythm did not change, but the fluctuations in gene expression was altered. Genes that are normally expressed in varying levels throughout a 24-hour cycle were expressed in high levels regardless of the time. In other words, the circadian rhythm remained the same, but its volume was steady and “loud” rather than increasing and decreasing in a rhythmic fashion.

Researchers believe that REV-ERBα may be the master volume knob that governs circadian rhythm strength. Senior author Ronald Evans, who is also director of Salk’s Gene Expression Laboratory, commented,

“Whether it is Beethoven’s 9th Symphony on your stereo or the symphony of genes in our bodies, both require volume to be heard. Our recent work describes how REV-ERBα acts as a molecular conductor to allows the volume or activity of thousands of genes to be dialed up or down.”

Amplitude Is Everything

This is the first time scientists have been able to experimentally affect circadian rhythm strength, but it appears to be a very important factor. Mice in this chronobiology study who were genetically altered to lack REV-ERBα developed a variety of serious health problems, including fatty liver disease. Too much of this protein also could have serious health effects. More research in this area will be needed but two things are clear: the amplitude, or volume, of our circadian rhythms appear to be extremely important to health, and this amplitude is at least partially controlled by the REV-ERBα protein.

The circadian rhythm is an integral part of the health of all organisms, so it makes sense that it would be tightly controlled in every way. This research opens up doors for new research on how circadian rhythm strength may be a factor affecting both internal clocks and whole body health.