Circadian rhythms regulate vital physiological and behavioral processes in most organisms. The highly accurate biological clock drives plants to flower at the right time and birds to migrate at the seasons change. The 24-hour period in humans and other animals is related to differential brain activity, sleep and wake cycles, feeding patterns – the list goes on.
“Clock” genes, such as clock (Clk) and period (Per), have been extensively studied in bacteria, fungi, plants, as wells as in animal models – Drosophila, mice, and humans. The maintenance of 24-hour clock requires a negative feedback loop, based on oscillations of “clock” proteins and an essential time delay at the end of each cycle. However, until now the nature of this delay was unclear. A novel study, published in the Current Biology, describes a microRNA-mediated mechanism for time delay in mammalian circadian clock.
MicroRNAs (miRNAs) are small non-coding molecules, responsible for the regulation of gene expression within cells. MiRNA-mediated control is largely achieved through post-transcriptional degradation of mRNA, the process known as RNA interference (RNAi). As a result, the amount of synthesized protein is reduced to an appropriate level, dependent on cell state.
The scientists demonstrate a significant speeding up of the cell’s internal clock by as much as 2 hours by disturbing the expression of miRNAs in cell culture and mice, and, therefore, the cascade of RNAi. In other words, you may now live 22-hour days instead of the 24-hours cycle. The effect is largely due to slower accumulation of some of the major circadian players – PER1 and PER2, suggesting the essential delay in the daily clock is mainly achieved through these proteins, which are dependent on miRNA-mediated expression. It should be noted that this mechanism is unique for mammals and is not conserved in other model animals, such as Drosophila.
The discovery of miRNA unique role in animal circadian clocks may open up new venues for studying sleep disorders, metabolic diseases, as well as understanding the topics like jet lag effects, seasonal depression or aging.