甲基化
精氨酸
生物
RNA剪接
甲基转移酶
选择性拼接
核糖核酸
蛋白质甲基化
蛋白质精氨酸甲基转移酶5
RNA结合蛋白
DNA甲基化
细胞生物学
生物化学
分子生物学
基因表达
基因
氨基酸
信使核糖核酸
作者
Wenjuan Li,Yaohui He,Jingjing Yang,Guo-Sheng Hu,Lin Yuan,Ting Ran,Bing‐ling Peng,Bing-Lan Xie,Ming‐Feng Huang,Xiang Gao,Haihua Huang,Helen He Zhu,Yan Feng,Wen Li
标识
DOI:10.1038/s41467-021-21963-1
摘要
Abstract Numerous 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.
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