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

doi:10.1038/ncomms7428

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 journal › Article › peer-review

163 Scopus citations

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 language	English (US)
Article number	6428
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms7428
State	Published - Mar 4 2015
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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title = "PRMT9 is a Type II methyltransferase that methylates the splicing factor SAP145",

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.",

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

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T1 - PRMT9 is a Type II methyltransferase that methylates the splicing factor SAP145

AU - Yang, Yanzhong

AU - Hadjikyriacou, Andrea

AU - Xia, Zheng

AU - Gayatri, Sitaram

AU - Kim, Daehoon

AU - Zurita-Lopez, Cecilia

AU - Kelly, Ryan

AU - Guo, Ailan

AU - Li, Wei

AU - Clarke, Steven G.

AU - Bedford, Mark T.

PY - 2015/3/4

Y1 - 2015/3/4

N2 - 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.

AB - 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.

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

Abstract

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