RNA,干细胞衰老 z-bo 2020-10-16 410

　　N6-methyladenine (m6A) is a relatively common type of eukaryotic RNA post-transcriptional apparent modification. Its establishment, elimination and recognition are m6A methyltransferase and demethylase and demethylase, respectively. Studies have shown that m6A is a key node in regulating gene expression, and participates in the regulation of many biological events by regulating the nuclear, stability, alternative splicing and translation of target RNA. In particular, it relates to the senescence of human stem cells. Research on the aging process is rarely reported. Therefore, it is necessary to further understand the dynamic changes, regulation and main regulatory factors of m6A during the aging process of human stem cells.

　　On October 9th, Qu Jing’s research team, the research team of Ci Weimin, a researcher of the Institute of Zoology, Chinese Academy of Sciences, and Zhang Weiqi, a researcher of the Beijing Institute of Genomics, Chinese Academy of Sciences, conducted a study on the stability of dependence of the team, Zhang Weiqi’s research team and animals Researcher Liu Guanghui 6Ac MIS12 mRNA research paper of the Institute of Science. In this study, we used pediatric and pre-adult human mesenchymal stem cells as a model to study the changes in RNA methylation modified m6A and its core methyltransferase METL3 during the aging process of human stem cells. Revealed the new mechanism of cell cycle factor MIS12, because the downstream effector of METL3/m6A regulates stem cell senescence. A study found that in human progeria mesenchymal stem cells, the level of m6A modification and the expression of its core methyltransferase METL3 were significantly down-regulated, and m6A modification was related to the regulation of human stem cell aging. Some suggestions may exist. At the same time, knocking out METL3 will cause the overall level of m6A to decrease and accelerate the senescence of human mesenchymal stem cells. On the other hand, the overexpression of METL3 can delay stem cell senescence, confirming the new role of METL3/m6A in regulating the senescence of human mesenchymal stem cells. In order to clarify the molecular mechanism of METL3/m6A that regulates cell senescence, the research team combined with molecular experiments to verify RNA methylation sequencing (MeRIP-seq) analysis, and used cell cycle regulator MIS12 as progeria stem cells. And it was found in stem cells lacking METL3. The level of m6A modification, gene expression and RNA stability are all significantly down-regulated, and the m6A binding protein IGF2BP2 can bind and stabilize MIS12 mRNA through m6A modification. Knockout of MIS12 or IGF2BP2 will accelerate the senescence of human mesenchymal stem cells. This study revealed the changes, regulation and main molecular targets of RNAm6A and its core methyltransferase METL3 during the aging process of human stem cells, and accelerated aging in terms of the epitranscriptome. Clarify the regulation mechanism, deepen your understanding of the new biological functions of METTTL3/m6A, and deepen your understanding of the epigenetic regulation mechanism of aging. In addition, this research also proposes the possibility of manipulating m6A and its catalytic enzymes to achieve aging intervention, new treatment ideas, and potential goals for delaying human aging and preventing aging-related diseases.