There is a cool clock in the human body - the biological clock. However, the mechanism by which the biological clock regulates physiological activities such as physiology, metabolism, and behavior is very complicated, and further research is needed. The reporter learned from Nanjing Agricultural University on the 15th that the team of Professor Wang Wei and the University of Chicago collaborated on the publication of research results in Cell Communication, revealing a new way of regulating the metabolism of the biological clock.
The biological clock is made of genes and proteins and is a gift of biological evolution. The biological clock controls the rhythm of our daily life: when to sleep peacefully, when to wake up mentally. Long-term circadian clock disorders can lead to metabolic diseases such as diabetes, hyperlipidemia, obesity, and even cancer. The 2017 Nobel Prize in Physiology and Medicine awarded three scientists who discovered the world's first clock gene.
N6-methyladenine (m6A) is the most abundant post-transcriptional modification on eukaryotic RNA, and plays an important regulatory role in gene expression, RNA splicing, mRNA trafficking and translation. Dynamic and reversible m6A methylation modifications are widely involved in mammalian development, immunity, tumorigenesis and metastasis, stem cell renewal, and fat differentiation. In this study, the researchers specifically knocked out the mouse liver clock gene Bmal1, found that the mouse liver lipid metabolism is abnormal, the mRNA m6A level is elevated, and the circadian rhythm is lost. Through m6A-seq, the researchers found that the m6A modification of PPARα, an important gene regulating liver lipid metabolism, was elevated, suggesting that Bmal1 affects m6A RNA methylation and regulates the expression of lipid metabolism-related genes to regulate lipid metabolism. Further studies confirmed that m6A RNA methylation modification can affect the stability and longevity of PPARα mRNA through YTHDF2, thereby regulating the transcription and translation of PPARα gene and affecting lipid metabolism. This study reveals a new way of regulating the metabolism of the circadian clock, expanding the understanding of the biological clock, m6A RNA methylation modification and metabolic relationship.