Independent transcriptomic and proteomic regulation by type I and II protein arginine methyltransferases

Maxim I. Maron; Stephanie M. Lehman; Sitaram Gayatri; Joseph D. DeAngelo; Subray Hegde; Benjamin M. Lorton; Yan Sun; Dina L. Bai; Simone Sidoli; Varun Gupta; Matthew R. Marunde; James R. Bone; Zu Wen Sun; Mark T. Bedford; Jeffrey Shabanowitz; Hongshan Chen; Donald F. Hunt; David Shechter

doi:10.1016/j.isci.2021.102971

Independent transcriptomic and proteomic regulation by type I and II protein arginine methyltransferases

Maxim I. Maron, Stephanie M. Lehman, Sitaram Gayatri, Joseph D. DeAngelo, Subray Hegde, Benjamin M. Lorton, Yan Sun, Dina L. Bai, Simone Sidoli, Varun Gupta, Matthew R. Marunde, James R. Bone, Zu Wen Sun, Mark T. Bedford, Jeffrey Shabanowitz, Hongshan Chen, Donald F. Hunt, David Shechter

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

Protein arginine methyltransferases (PRMTs) catalyze the post-translational monomethylation (Rme1), asymmetric (Rme2a), or symmetric (Rme2s) dimethylation of arginine. To determine the cellular consequences of type I (Rme2a) and II (Rme2s) PRMTs, we developed and integrated multiple approaches. First, we determined total cellular dimethylarginine levels, revealing that Rme2s was ∼3% of total Rme2 and that this percentage was dependent upon cell type and PRMT inhibition status. Second, we quantitatively characterized in vitro substrates of the major enzymes and expanded upon PRMT substrate recognition motifs. We also compiled our data with publicly available methylarginine-modified residues into a comprehensive database. Third, we inhibited type I and II PRMTs and performed proteomic and transcriptomic analyses to reveal their phenotypic consequences. These experiments revealed both overlapping and independent PRMT substrates and cellular functions. Overall, this study expands upon PRMT substrate diversity, the arginine methylome, and the complex interplay of type I and II PRMTs.

Original language	English (US)
Article number	102971
Journal	iScience
Volume	24
Issue number	9
DOIs	https://doi.org/10.1016/j.isci.2021.102971
State	Published - Sep 24 2021

Keywords

cell biology
molecular biology

ASJC Scopus subject areas

General

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10.1016/j.isci.2021.102971

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Maron, M. I., Lehman, S. M., Gayatri, S., DeAngelo, J. D., Hegde, S., Lorton, B. M., Sun, Y., Bai, D. L., Sidoli, S., Gupta, V., Marunde, M. R., Bone, J. R., Sun, Z. W., Bedford, M. T., Shabanowitz, J., Chen, H., Hunt, D. F., & Shechter, D. (2021). Independent transcriptomic and proteomic regulation by type I and II protein arginine methyltransferases. iScience, 24(9), Article 102971. https://doi.org/10.1016/j.isci.2021.102971

Maron, MI, Lehman, SM, Gayatri, S, DeAngelo, JD, Hegde, S, Lorton, BM, Sun, Y, Bai, DL, Sidoli, S , Gupta, V, Marunde, MR, Bone, JR, Sun, ZW, Bedford, MT, Shabanowitz, J, Chen, H, Hunt, DF & Shechter, D 2021, 'Independent transcriptomic and proteomic regulation by type I and II protein arginine methyltransferases', iScience, vol. 24, no. 9, 102971. https://doi.org/10.1016/j.isci.2021.102971

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title = "Independent transcriptomic and proteomic regulation by type I and II protein arginine methyltransferases",

abstract = "Protein arginine methyltransferases (PRMTs) catalyze the post-translational monomethylation (Rme1), asymmetric (Rme2a), or symmetric (Rme2s) dimethylation of arginine. To determine the cellular consequences of type I (Rme2a) and II (Rme2s) PRMTs, we developed and integrated multiple approaches. First, we determined total cellular dimethylarginine levels, revealing that Rme2s was ∼3% of total Rme2 and that this percentage was dependent upon cell type and PRMT inhibition status. Second, we quantitatively characterized in vitro substrates of the major enzymes and expanded upon PRMT substrate recognition motifs. We also compiled our data with publicly available methylarginine-modified residues into a comprehensive database. Third, we inhibited type I and II PRMTs and performed proteomic and transcriptomic analyses to reveal their phenotypic consequences. These experiments revealed both overlapping and independent PRMT substrates and cellular functions. Overall, this study expands upon PRMT substrate diversity, the arginine methylome, and the complex interplay of type I and II PRMTs.",

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author = "Maron, {Maxim I.} and Lehman, {Stephanie M.} and Sitaram Gayatri and DeAngelo, {Joseph D.} and Subray Hegde and Lorton, {Benjamin M.} and Yan Sun and Bai, {Dina L.} and Simone Sidoli and Varun Gupta and Marunde, {Matthew R.} and Bone, {James R.} and Sun, {Zu Wen} and Bedford, {Mark T.} and Jeffrey Shabanowitz and Hongshan Chen and Hunt, {Donald F.} and David Shechter",

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T1 - Independent transcriptomic and proteomic regulation by type I and II protein arginine methyltransferases

AU - Maron, Maxim I.

AU - Lehman, Stephanie M.

AU - Gayatri, Sitaram

AU - DeAngelo, Joseph D.

AU - Hegde, Subray

AU - Lorton, Benjamin M.

AU - Sun, Yan

AU - Bai, Dina L.

AU - Sidoli, Simone

AU - Gupta, Varun

AU - Marunde, Matthew R.

AU - Bone, James R.

AU - Sun, Zu Wen

AU - Bedford, Mark T.

AU - Shabanowitz, Jeffrey

AU - Chen, Hongshan

AU - Hunt, Donald F.

AU - Shechter, David

PY - 2021/9/24

Y1 - 2021/9/24

N2 - Protein arginine methyltransferases (PRMTs) catalyze the post-translational monomethylation (Rme1), asymmetric (Rme2a), or symmetric (Rme2s) dimethylation of arginine. To determine the cellular consequences of type I (Rme2a) and II (Rme2s) PRMTs, we developed and integrated multiple approaches. First, we determined total cellular dimethylarginine levels, revealing that Rme2s was ∼3% of total Rme2 and that this percentage was dependent upon cell type and PRMT inhibition status. Second, we quantitatively characterized in vitro substrates of the major enzymes and expanded upon PRMT substrate recognition motifs. We also compiled our data with publicly available methylarginine-modified residues into a comprehensive database. Third, we inhibited type I and II PRMTs and performed proteomic and transcriptomic analyses to reveal their phenotypic consequences. These experiments revealed both overlapping and independent PRMT substrates and cellular functions. Overall, this study expands upon PRMT substrate diversity, the arginine methylome, and the complex interplay of type I and II PRMTs.

AB - Protein arginine methyltransferases (PRMTs) catalyze the post-translational monomethylation (Rme1), asymmetric (Rme2a), or symmetric (Rme2s) dimethylation of arginine. To determine the cellular consequences of type I (Rme2a) and II (Rme2s) PRMTs, we developed and integrated multiple approaches. First, we determined total cellular dimethylarginine levels, revealing that Rme2s was ∼3% of total Rme2 and that this percentage was dependent upon cell type and PRMT inhibition status. Second, we quantitatively characterized in vitro substrates of the major enzymes and expanded upon PRMT substrate recognition motifs. We also compiled our data with publicly available methylarginine-modified residues into a comprehensive database. Third, we inhibited type I and II PRMTs and performed proteomic and transcriptomic analyses to reveal their phenotypic consequences. These experiments revealed both overlapping and independent PRMT substrates and cellular functions. Overall, this study expands upon PRMT substrate diversity, the arginine methylome, and the complex interplay of type I and II PRMTs.

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Independent transcriptomic and proteomic regulation by type I and II protein arginine methyltransferases

Abstract

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