2. Academic Validation
  3. Profiling PRMT methylome reveals roles of hnRNPA1 arginine methylation in RNA splicing and cell growth

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

  • Nat Commun. 2021 Mar 29;12(1):1946. doi: 10.1038/s41467-021-21963-1.
Wen-Juan Li  # 1 2,  Yao-Hui He  # 1 2,  Jing-Jing Yang  # 1 2,  Guo-Sheng Hu 1 2,  Yi-An Lin 1 2,  Ting Ran 1 2,  Bing-Ling Peng 1 2,  Bing-Lan Xie 1 2,  Ming-Feng Huang 1 2,  Xiang Gao 2,  Hai-Hua Huang 3,  Helen He Zhu 4,  Feng Ye 5,  Wen Liu 6 7 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China.
  • 2 Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China.
  • 3 Department of Pathology, The Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, China.
  • 4 Department of Urology, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
  • 5 Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Fujian, China.
  • 6 State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China. w2liu@xmu.edu.cn.
  • 7 Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China. w2liu@xmu.edu.cn.
  • 8 State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China. w2liu@xmu.edu.cn.
  • # Contributed equally.
PMID: 33782401 DOI: 10.1038/s41467-021-21963-1
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.

Figures
Products