Junjie Zhang and Xiaotian Zhang research team revealed the regulatory effect of NSUN2-mediated ATX mRNA methylation on tumor cell migration
5-methylcytosine (m5C) modification is one of the vital ways in mRNA post-transcriptional regulation, and it plays an important role in many physiological and pathological processes, like embryonic development, cell senescence and tumor. Autotaxin (ATX) is a secreted glycoprotein that can catalyze the conversion of lysophosphatidylcholine to lysophosphatidic acid (LPA). The ATX-LPA axis is involved in the regulation of various crucial life activities, such as cell survival, migration, proliferation and differentiation. The research of Professor Zhang Junjie and Associate Professor Zhang Xiaotian’s team found that RNA methyltransferase NSUN2 catalyzed the m5C modification in ATX mRNA 3'UTR. This epigenetic modification of RNA could promote the ALYREF-mediated nuclear export of ATX mRNA and improve the translation of ATX mRNA, thereby up-regulating the expression level of ATX. Knockdown of NSUN2 significantly reduced the expression of ATX in glioma cell line U87 and inhibited the migration of U87 cells, while the addition of LPA could rescue the migration ability, indicating that the NSUN2-ATX-LPA pathway has a regulatory effect on tumor cell migration. This study revealed, for the first time, the role of RNA modification in the regulation of lysophospholipid metabolism. The research results were published in the Journal of Biological Chemistry on December 25, 2020, entitled "NSun2 promotes cell migration through methylating autotaxin mRNA". Professor Zhang Junjie and Associate Professor Zhang Xiaotian are the co-corresponding authors, and Dr. Xu Xin is the first author of this paper. This research was funded by the National Natural Science Foundation of China, the Beijing Municipal Natural Science Foundation and the Key Laboratory of Cell Proliferation and Regulation Biology of the Ministry of Education.
Paper’s full-text link: https://www.jbc.org/content/295/52/18134.full.pdf.