Epigenetic Timekeepers: Dissecting the Role of Non-Coding RNAs in Circadian Rhythm Plasticity Across Cell Types

While classic circadian rhythm research has focused on well-known clock genes (like BMAL1, PER, and CLOCK), there’s growing but still underexplored evidence that non-coding RNAs (ncRNAs, including microRNAs and lncRNAs) modulate circadian processes at the post-transcriptional level. Previous reviews (e.g., Jenwitheesuk et al., 2014) highlight epigenetics and metabolism, but the specific, dynamic roles of ncRNAs across different tissues remain a black box. Using single-cell RNA sequencing (as in Huang et al., 2024 for hepatocytes), we could map rhythmic ncRNA expression across organs. Then, CRISPR interference or activation could selectively modulate candidate ncRNAs in a tissue-specific manner, revealing their impact on circadian plasticity and resilience to misalignment (like in shift work or disease). This approach bridges molecular, epigenetic, and systems-level circadian biology, with huge implications for chronotherapy and personalized medicine.

References:

1. Circadian Rhythm Disruption in Hepatocellular Carcinoma Investigated by Integrated Analysis of Bulk and Single-Cell RNA Sequencing Data. Lien-Hung Huang, Chun-Ying Huang, Yueh-Wei Liu, P. Chien, Ting-Min Hsieh, Hang-Tsung Liu, Hui-Ping Lin, Chia-Jung Wu, Pei-Chin Chuang, Ching-Hua Hsieh (2024). International Journal of Molecular Sciences.
2. Melatonin Regulates Aging and Neurodegeneration through Energy Metabolism, Epigenetics, Autophagy and Circadian Rhythm Pathways. Anorut Jenwitheesuk, Chutikorn Nopparat, S. Mukda, P. Wongchitrat, P. Govitrapong (2014). International Journal of Molecular Sciences.