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

Wen-juan Li, Yao-hui He, Jing-jing Yang, Guo-sheng Hu, Yi-an Lin, Ting Ran, Bing-ling Peng, Bing-lan Xie, Ming-feng Huang, Xiang Gao, Hai-hua Huang, Helen He Zhu, Feng Ye and Wen Liu ()
Additional contact information
Wen-juan Li: Xiamen University
Yao-hui He: Xiamen University
Jing-jing Yang: Xiamen University
Guo-sheng Hu: Xiamen University
Yi-an Lin: Xiamen University
Ting Ran: Xiamen University
Bing-ling Peng: Xiamen University
Bing-lan Xie: Xiamen University
Ming-feng Huang: Xiamen University
Xiang Gao: Xiamen University
Hai-hua Huang: Shantou University Medical College
Helen He Zhu: Shanghai Jiao Tong University
Feng Ye: The First Affiliated Hospital of Xiamen University
Wen Liu: Xiamen University

Nature Communications, 2021, vol. 12, issue 1, 1-20

Abstract: 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.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-21963-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21963-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-21963-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().