After more than a decade of research, a team led by Drs. Deborah Bell-Pedersen and Teresa Lamb in the Department of Biology at Texas A&M University, has uncovered how the body’s internal clock fine-tunes the cellular machinery responsible for making proteins.
The study, published in Cell Reports, demonstrates that the circadian clock rhythmically alters the composition of ribosomes - the molecular machines that translate genetic information into proteins. These daily changes, the researchers found, regulate both when proteins are produced and how accurately they are synthesized.
Using the model organism Neurospora crassa, the team discovered that levels of specific ribosomal proteins in ribosomes, including eL31, fluctuate with circadian time and directly influence daily rhythms in cellular protein production. A surprising discovery was that clock-regulated incorporation of eL31 into ribosomes affects the accuracy of protein synthesis, linking temporal ribosome remodeling to daily changes in protein diversity that extend beyond the static genetic blueprint.
“These findings reveal that the circadian clock doesn’t just control when protein levels peak, but also how it expands the functional diversity of proteins beyond the encoded genome sequence,” said Bell-Pedersen. “By uncovering how the clock influences translation at the molecular level, we open doors to understanding how disruptions in circadian rhythms, such as those caused by shift work or jet lag, might contribute to diseases involving protein levels or protein synthesis accuracy.”
The work provides a new understanding of how timing mechanisms within cells influence nearly every aspect of biology. Because protein synthesis fidelity is critical for cellular homeostasis and longevity, the study suggests that circadian regulation helps balance translational accuracy to maintain proteostasis, particularly under stress. As clock function declines with age, this regulation may falter, increasing protein errors and driving age-related disease. Preserving circadian clock function could therefore enhance protein quality control and promote healthy aging.