Molecular circadian clocks are crucial to many aspects of human health. For decades, researchers have been trying to identify what makes these clocks tick. In a new study, published in PNAS, researchers have discovered a new cog in the circadian clock – microRNAs (miRNAs).
Circadian clocks exist in cells throughout the body and govern many aspects of human health. Researchers hope that further study of these clocks will provide new insights into diseases like Alzheimer’s, cancer and diabetes. Previously, most research has focussed on clock genes, which encode proteins that drive oscillating cycles of gene expression affecting physiology and behaviour. The regulatory modules involving noncoding RNAs are less thoroughly understood. Past research has indicated that miRNAs may have a role in the function of circadian clocks. Nonetheless, determining which of the hundreds of miRNAs in the genome are important remains unclear.
Role of microRNAs
To identify miRNAs that have the potential to modulate circadian rhythms, researchers conducted a genome-wide miRNA screen using U2OS luciferase reported cells based on the cell’s 24-hour circadian clock cycle. Among 989 miRNAs in the library, the team specifically found that 120 changed the period length in a dose-dependent manner.
The researchers specifically focussed on the miR-183/96/182 cluster among the candidate miRNA hits. Here, they identified their circadian function both in vitro and in vivo. They found that all three members of this miRNA cluster can modulate circadian rhythms. Specifically, they discovered that miR-96 directly targeted a core circadian clock gene, PER2. Additionally, knockout of the miR-183/96/182 cluster in mice impacted brain, retina and lung tissue in different ways. This indicates that the way miRNAs regulate the circadian clock is tissue specific. Understanding the impact of miRNAs on the circadian clock in individual tissues could be important for gaining insights into new ways of treating or preventing specific diseases.
Steve Kay, Provost Professor of neurology, biomedical engineering and quantitative computational biology at the Keck School of Medicine of USC, stated:
“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.
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.”
Image credit: By D3Damon – canva.com