A key component of the circadian clock is a transcriptional-translational feedback loop involving several clock genes. The positive elements of this loop, CLOCK and BMAL1, form a complex that activates the transcription of the negative elements, such as PER and CRY. PER and CRY proteins accumulate in the cytoplasm and eventually inhibit CLOCK-BMAL1 activity, thus completing the feedback loop. Additional feedback loops and post-translational modifications contribute to the robustness and accuracy of the circadian clock.
Research in the past decade has identified a small RNA molecule, miR-219, as a potential regulator of the circadian clock. miR-219 directly targets the transcript of PER1, one of the negative elements of the feedback loop. Overexpression of miR-219 has been shown to disrupt the circadian rhythm in mouse fibroblasts and liver cells. Interestingly, miR-219 levels are regulated by the circadian clock, suggesting a reciprocal regulatory relationship between the two.
However, it is important to note that miR-219 is just one piece of the complex circadian clock puzzle and does not entirely explain the intricacies of circadian regulation. Further research is needed to fully understand the interplay between miR-219 and the other components of the circadian clock and how they contribute to the temporal coordination of physiological processes.
