PRMT9 is a Type II methyltransferase that methylates the splicing factor SAP145

Yanzhong Yang, Andrea Hadjikyriacou, Zheng Xia, Sitaram Gayatri, Daehoon Kim, Cecilia Zurita-Lopez, Ryan Kelly, Ailan Guo, Wei Li, Steven G. Clarke, Mark T. Bedford

Research output: Contribution to journalArticle

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Abstract

The human genome encodes a family of nine protein arginine methyltransferases (PRMT1-9), whose members can catalyse three distinct types of methylation on arginine residues. Here we identify two spliceosome-associated proteins - SAP145 and SAP49 - as PRMT9-binding partners, linking PRMT9 to U2 snRNP maturation. We show that SAP145 is methylated by PRMT9 at arginine 508, which takes the form of monomethylated arginine (MMA) and symmetrically dimethylated arginine (SDMA). PRMT9 thus joins PRMT5 as the only mammalian enzymes capable of depositing the SDMA mark. Methylation of SAP145 on Arg 508 generates a binding site for the Tudor domain of the Survival of Motor Neuron (SMN) protein, and RNA-seq analysis reveals gross splicing changes when PRMT9 levels are attenuated. These results identify PRMT9 as a nonhistone methyltransferase that primes the U2 snRNP for interaction with SMN.

Original languageEnglish (US)
Article number6428
JournalNature Communications
Volume6
DOIs
StatePublished - Mar 4 2015
Externally publishedYes

Fingerprint

Phosphatidyl-N-Methylethanolamine N-Methyltransferase
splicing
Arginine
methylation
proteins
neurons
U2 Small Nuclear Ribonucleoproteins
Methylation
Motor Neurons
genome
Neurons
Protein-Arginine N-Methyltransferases
enzymes
Spliceosomes
Methyltransferases
Human Genome
Proteins
Genes
Binding Sites
RNA Splicing Factors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Yang, Y., Hadjikyriacou, A., Xia, Z., Gayatri, S., Kim, D., Zurita-Lopez, C., ... Bedford, M. T. (2015). PRMT9 is a Type II methyltransferase that methylates the splicing factor SAP145. Nature Communications, 6, [6428]. https://doi.org/10.1038/ncomms7428

PRMT9 is a Type II methyltransferase that methylates the splicing factor SAP145. / Yang, Yanzhong; Hadjikyriacou, Andrea; Xia, Zheng; Gayatri, Sitaram; Kim, Daehoon; Zurita-Lopez, Cecilia; Kelly, Ryan; Guo, Ailan; Li, Wei; Clarke, Steven G.; Bedford, Mark T.

In: Nature Communications, Vol. 6, 6428, 04.03.2015.

Research output: Contribution to journalArticle

Yang, Y, Hadjikyriacou, A, Xia, Z, Gayatri, S, Kim, D, Zurita-Lopez, C, Kelly, R, Guo, A, Li, W, Clarke, SG & Bedford, MT 2015, 'PRMT9 is a Type II methyltransferase that methylates the splicing factor SAP145', Nature Communications, vol. 6, 6428. https://doi.org/10.1038/ncomms7428
Yang, Yanzhong ; Hadjikyriacou, Andrea ; Xia, Zheng ; Gayatri, Sitaram ; Kim, Daehoon ; Zurita-Lopez, Cecilia ; Kelly, Ryan ; Guo, Ailan ; Li, Wei ; Clarke, Steven G. ; Bedford, Mark T. / PRMT9 is a Type II methyltransferase that methylates the splicing factor SAP145. In: Nature Communications. 2015 ; Vol. 6.
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