Molecular cell: a new mechanism of mTOR inhibiting miRNA synthesis discovered by Chinese scientists

February 3, 2015 / BIOON / -- recently, the International Journal of molecular biology, molecular cell, published online pan, a Chinese scientist According to the latest research results of Zheng research team, they found that when the living environment of cells changes, cells can regulate the biosynthesis of miRNA that inhibits apoptosis through mtor1-mdm2-drosha signal pathway, so as to maintain cell survival This study reveals the relationship between mTOR and miRNA synthesis for the first time, and provides a possible molecular mechanism for understanding the role of mTOR in energy and apoptosis The researchers point out that mTOR is a very important molecule that can sense the nutrition and energy state of cells, and then regulate cell survival and metabolism to cope with environmental changes Peiying Ye et al Were surprised to find that when the negative regulatory factor TSC1 of mTORC1 was mutated, a large number of miRNA expression decreased in Drosha degradation, and when the important component Raptor of mTORC1 complex was mutated, the synthesis of miRNA in cells could be increased The researchers further explored the mechanism and found that when mTORC1 complex is activated, it can promote the expression of MDM2 As E3 ubiquitin ligase of Drosha, MDM2 further promotes the ubiquitin degradation process of Drosha Drosha is a gene induced and expressed in the state of nutrition and energy deficiency, which can promote cells to resist the adverse effects of glucose deficiency Through high-throughput screening of the miRNA library, the researchers found that four miRNAs can promote cell resistance to glucose deficiency induced apoptosis, and through experiments, it is confirmed that this protection is regulated by mtorc1-mdm2-drosha signal pathway In conclusion, mTORC1 was found to be able to sense changes in nutritional status, promote Drosha ubiquitination and degradation by activating MDM2 expression, and further inhibit miRNA synthesis The results of this study link mTOR with miRNA synthesis process, and provide a possible molecular mechanism for explaining the role of mTOR between energy and apoptosis This article is the original compilation of Biovalley, welcome to reprint! Please indicate the source of the reprint and attach the original link Thank you!
doi:10.1016/j.molcel.2014.12.034
An mTORC1-Mdm2-Drosha Axis for miRNA Biogenesis in Response to Glucose- and Amino Acid-Deprivation
Peiying Ye, Yu Liu, Chong Chen, Fei Tang, Qi Wu, Xiang Wang, Chang-Gong Liu, Xiuping Liu, Runhua Liu, Yang Liu , Pan Zheng
mTOR senses nutrient and energy status to regulate cell survival and metabolism in response to environmental changes Surprisingly, targeted mutation of Tsc1, a negative regulator of mTORC1, caused a broad reduction in miRNAs due to Drosha degradation Conversely, targeted mutation of Raptor, an essential component of mTORC1, increased miRNA biogenesis mTOR activation increased expression of Mdm2, which is hereby identified as the necessary and sufficient ubiquitin E3 ligase for Drosha Drosha was induced by nutrient and energy deprivation and conferred resistance to glucose deprivation Using a high-throughput screen of a miRNA library, we identified four miRNAs that were necessary and sufficient to protect cells against glucose-deprivation-induced apoptosis These miRNA was regulated by glucose through the mTORC1-MDM2-DROSHA axis Taken together, our data reveal an mTOR-Mdm2-Drosha pathway in mammalian cells that broadly regulates miRNA biogenesis as a response to alteration in cellular environment