Profiling PRMT methylome reveals roles of hnRNPA1 arginine methylation in RNA splicing and cell growth.
Nat Commun
; 12(1): 1946, 2021 03 29.
Article
em En
| MEDLINE
| ID: mdl-33782401
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Proteína-Arginina N-Metiltransferases
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Neoplasias da Mama
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Neoplasias Colorretais
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Ribonucleoproteína Nuclear Heterogênea A1
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article