Profiling PRMT methylome reveals roles of hnRNPA1 arginine methylation in RNA splicing and cell growth


Li Wen-juan,He Yao-huiORCID,Yang Jing-jing,Hu Guo-sheng,Lin Yi-an,Ran Ting,Peng Bing-ling,Xie Bing-lan,Huang Ming-feng,Gao Xiang,Huang Hai-hua,Zhu Helen HeORCID,Ye Feng,Liu WenORCID


AbstractNumerous substrates have been identified for Type I and II arginine methyltransferases (PRMTs). However, the full substrate spectrum of the only type III PRMT, PRMT7, and its connection to type I and II PRMT substrates remains unknown. Here, we use mass spectrometry to reveal features of PRMT7-regulated methylation. We find that PRMT7 predominantly methylates a glycine and arginine motif; multiple PRMT7-regulated arginine methylation sites are close to phosphorylations sites; methylation sites and proximal sequences are vulnerable to cancer mutations; and methylation is enriched in proteins associated with spliceosome and RNA-related pathways. We show that PRMT4/5/7-mediated arginine methylation regulates hnRNPA1 binding to RNA and several alternative splicing events. In breast, colorectal and prostate cancer cells, PRMT4/5/7 are upregulated and associated with high levels of hnRNPA1 arginine methylation and aberrant alternative splicing. Pharmacological inhibition of PRMT4/5/7 suppresses cancer cell growth and their co-inhibition shows synergistic effects, suggesting them as targets for cancer therapy.


National Natural Science Foundation of China


Springer Science and Business Media LLC


General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry







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