The production of more than 1,000 proteins in clock cells occurs predominantly during the middle of the day or middle of the night
BOSTON (November 5, 2013, 5:00 p.m. EST) —Sleep disorders are reported to affect 50 to 70 million Americans, and have been linked to obesity and diabetes, as well as depression and other psychiatric disorders. Circadian cycles are driven by biological clocks that regulate behaviors such as sleep. Environmental or genetic alterations of the circadian clock contribute to jet lag, sleep disorders, and psychiatric disorders.
In a new study published 5 November in the open access journal PLOS Biology, Rob Jackson, who is professor at Tufts University School of Medicine (TUSM) and member of the neuroscience and genetics faculties at the Sackler School of Graduate Biomedical Sciences at Tufts, and colleagues have examined a large group of rhythmically produced proteins in cells that make up the circadian clock (also called clock cells) of the fruit fly Drosophila. Surprisingly, they find that a majority of the proteins are produced during two intervals of the circadian cycle, the middle of the day or middle of the night.
“The circadian clocks of fruit flies and humans share molecular components, making the fruit fly an outstanding model for genetic studies focused on circadian behavior,” said first author Yanmei Huang, research assistant professor of neuroscience at TUSM and a member of Jackson’s team.
This study uses an innovative ribosome profiling technique to reveal the complete circadian program of protein synthesis (the ‘circadian translatome’) within these clock cells. Fruit flies were collected at different times of the circadian cycle, and mRNAs bound to ribosomes were isolated from clock cells; they were identified and quantified using RNA sequencing methods to document patterns in protein production.
Messenger RNAs (mRNAs) carry instructions for protein production in a process called translation. Jackson’s team used translational profiling, a method that indirectly reveals the production of proteins, and RNA sequencing to determine exactly when proteins in clock cells are produced from mRNAs. They identified 1,069 mRNAs, including hundreds of novel mRNAs that show peaks in translation at certain times of the day.
Proteins formed from these 1,069 mRNAs were classified by their biological function. Among the proteins whose functions are known, the researchers found that proteins required for similar functions were produced at the same times. Proteins required for metabolism show peak production during the day, while proteins required for cell growth show peak production during the night.
The researchers hope that by identifying the specific times proteins are produced in clock cells and their functions, they can better understand how the circadian clock regulates protein production and the body’s biological systems. This, in turn, will provide insight into diseases and psychiatric disorders caused by disruptions in the circadian system.
“This highly synchronized protein production is a novel discovery. For the first time in any organism, we identified proteins within clock cells that show 24-hour rhythms of production,” said senior author Rob Jackson.
Jackson’s research in Drosophila has focused on genes and neural circuits that regulate circadian behavior. Some of his other recent work, in collaboration with postdoctoral associate Dr. Fanny S. Ng showed that astrocytes, a type of glial cell in the brain, are critical in regulating circadian rhythms.
Additional authors of the study are Joshua A. Ainsley, postdoctoral scholar in neuroscience at TUSM, and Leon G. Reijmers, assistant professor of neuroscience at TUSM and member of the neuroscience program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts.
Research reported in this publication was supported by the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Neurological Disorders and Stroke (NINDS), both of the National Institutes of Health under award numbers R01HL059873 and R01NS065900, respectively. The Tufts Center for Neuroscience Research was funded by NINDS under award number P30NS047243. Yanmei Huang, Ph.D., was supported by a Young Investigator Award from the Brain & Behavior Research Foundation (award number NARSAD17339). Leon G. Reijmers, Ph.D., was supported by an NIH Director’s New Innovator Award from the Office of the Director at the National Institutes of Health under award number DP2OD006446.
Huang Y, Ainsley JA, Reijmers LG, Jackson FR (2013) Translational Profiling of Clock Cells Reveals Circadianly Synchronized Protein Synthesis. PLoS Biol 11(11): e1001703. doi:10.1371/journal.pbio.1001703
About Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences
Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts University are international leaders in innovative medical and population health education and advanced research. Tufts University School of Medicine emphasizes rigorous fundamentals in a dynamic learning environment to educate physicians, scientists, and public health professionals to become leaders in their fields. The School of Medicine and the Sackler School are renowned for excellence in education in general medicine, the biomedical sciences, and public health, as well as for innovative research at the cellular, molecular, and population health level. Ranked among the top in the nation, the School of Medicine is affiliated with six major teaching hospitals and more than 30 health care facilities. Tufts University School of Medicine and the Sackler School undertake research that is consistently rated among the highest in the nation for its effect on the advancement of medical and prevention science.
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A note regarding the above references to the Sackler School: In December 2019, Tufts University announced that it would remove the Sackler name from all programs and facilities—including the Sackler School of Graduate Biomedical Sciences. At that time, the school was renamed the Graduate School of Biomedical Sciences.
