Proteomic analysis of arginine methylation sites in human cells reveals dynamic regulation during transcriptional arrest

Research output: Contribution to journalJournal articlepeer-review

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Proteomic analysis of arginine methylation sites in human cells reveals dynamic regulation during transcriptional arrest. / Sylvestersen, Kathrine B; Horn, Heiko; Jungmichel, Stephanie; Jensen, Lars J; Nielsen, Michael L.

In: Molecular & Cellular Proteomics, Vol. 13, 21.02.2014, p. 2072-2088.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Sylvestersen, KB, Horn, H, Jungmichel, S, Jensen, LJ & Nielsen, ML 2014, 'Proteomic analysis of arginine methylation sites in human cells reveals dynamic regulation during transcriptional arrest', Molecular & Cellular Proteomics, vol. 13, pp. 2072-2088. https://doi.org/10.1074/mcp.O113.032748

APA

Sylvestersen, K. B., Horn, H., Jungmichel, S., Jensen, L. J., & Nielsen, M. L. (2014). Proteomic analysis of arginine methylation sites in human cells reveals dynamic regulation during transcriptional arrest. Molecular & Cellular Proteomics, 13, 2072-2088. https://doi.org/10.1074/mcp.O113.032748

Vancouver

Sylvestersen KB, Horn H, Jungmichel S, Jensen LJ, Nielsen ML. Proteomic analysis of arginine methylation sites in human cells reveals dynamic regulation during transcriptional arrest. Molecular & Cellular Proteomics. 2014 Feb 21;13:2072-2088. https://doi.org/10.1074/mcp.O113.032748

Author

Sylvestersen, Kathrine B ; Horn, Heiko ; Jungmichel, Stephanie ; Jensen, Lars J ; Nielsen, Michael L. / Proteomic analysis of arginine methylation sites in human cells reveals dynamic regulation during transcriptional arrest. In: Molecular & Cellular Proteomics. 2014 ; Vol. 13. pp. 2072-2088.

Bibtex

@article{979d1a5d06734ba7a6d725e7a5fd76ca,
title = "Proteomic analysis of arginine methylation sites in human cells reveals dynamic regulation during transcriptional arrest",
abstract = "The covalent attachment of methyl groups to the side-chain of arginine residues is known to play essential roles in regulation of transcription, protein function and RNA metabolism. The specific N-methylation of arginine residues is catalyzed by a small family of gene products known as protein arginine methyltransferases; however, very little is known about which arginine residues become methylated on target substrates. Here we describe a proteomics methodology that combines single-step immunoenrichment of methylated peptides with high-resolution mass spectrometry to identify endogenous arginine mono-methylation (MMA) sites. We thereby identify 1,027 site-specific MMA sites on 494 human proteins, discovering numerous novel mono-methylation targets and confirming the majority of currently known MMA substrates. Nuclear RNA-binding proteins involved in RNA processing, RNA localization, transcription, and chromatin remodeling are predominantly found modified with MMA. Despite this, MMA sites prominently are located outside RNA-binding domains as compared to the proteome-wide distribution of arginine residues. Quantification of arginine methylation in cells treated with Actinomycin D uncovers strong site-specific regulation of MMA sites during transcriptional arrest. Interestingly, several MMA sites are down-regulated after a few hours of transcriptional arrest. In contrast, the corresponding di-methylation or protein expression level is not altered in expression, confirming that MMA sites contain regulated functions on their own. Collectively, we present a site-specific MMA dataset in human cells and demonstrate for the first time that MMA is a dynamic post-translational modification regulated during transcriptional arrest by a hitherto uncharacterized arginine demethylase.",
author = "Sylvestersen, {Kathrine B} and Heiko Horn and Stephanie Jungmichel and Jensen, {Lars J} and Nielsen, {Michael L}",
year = "2014",
month = feb,
day = "21",
doi = "10.1074/mcp.O113.032748",
language = "English",
volume = "13",
pages = "2072--2088",
journal = "Molecular and Cellular Proteomics",
issn = "1535-9476",
publisher = "American Society for Biochemistry and Molecular Biology",

}

RIS

TY - JOUR

T1 - Proteomic analysis of arginine methylation sites in human cells reveals dynamic regulation during transcriptional arrest

AU - Sylvestersen, Kathrine B

AU - Horn, Heiko

AU - Jungmichel, Stephanie

AU - Jensen, Lars J

AU - Nielsen, Michael L

PY - 2014/2/21

Y1 - 2014/2/21

N2 - The covalent attachment of methyl groups to the side-chain of arginine residues is known to play essential roles in regulation of transcription, protein function and RNA metabolism. The specific N-methylation of arginine residues is catalyzed by a small family of gene products known as protein arginine methyltransferases; however, very little is known about which arginine residues become methylated on target substrates. Here we describe a proteomics methodology that combines single-step immunoenrichment of methylated peptides with high-resolution mass spectrometry to identify endogenous arginine mono-methylation (MMA) sites. We thereby identify 1,027 site-specific MMA sites on 494 human proteins, discovering numerous novel mono-methylation targets and confirming the majority of currently known MMA substrates. Nuclear RNA-binding proteins involved in RNA processing, RNA localization, transcription, and chromatin remodeling are predominantly found modified with MMA. Despite this, MMA sites prominently are located outside RNA-binding domains as compared to the proteome-wide distribution of arginine residues. Quantification of arginine methylation in cells treated with Actinomycin D uncovers strong site-specific regulation of MMA sites during transcriptional arrest. Interestingly, several MMA sites are down-regulated after a few hours of transcriptional arrest. In contrast, the corresponding di-methylation or protein expression level is not altered in expression, confirming that MMA sites contain regulated functions on their own. Collectively, we present a site-specific MMA dataset in human cells and demonstrate for the first time that MMA is a dynamic post-translational modification regulated during transcriptional arrest by a hitherto uncharacterized arginine demethylase.

AB - The covalent attachment of methyl groups to the side-chain of arginine residues is known to play essential roles in regulation of transcription, protein function and RNA metabolism. The specific N-methylation of arginine residues is catalyzed by a small family of gene products known as protein arginine methyltransferases; however, very little is known about which arginine residues become methylated on target substrates. Here we describe a proteomics methodology that combines single-step immunoenrichment of methylated peptides with high-resolution mass spectrometry to identify endogenous arginine mono-methylation (MMA) sites. We thereby identify 1,027 site-specific MMA sites on 494 human proteins, discovering numerous novel mono-methylation targets and confirming the majority of currently known MMA substrates. Nuclear RNA-binding proteins involved in RNA processing, RNA localization, transcription, and chromatin remodeling are predominantly found modified with MMA. Despite this, MMA sites prominently are located outside RNA-binding domains as compared to the proteome-wide distribution of arginine residues. Quantification of arginine methylation in cells treated with Actinomycin D uncovers strong site-specific regulation of MMA sites during transcriptional arrest. Interestingly, several MMA sites are down-regulated after a few hours of transcriptional arrest. In contrast, the corresponding di-methylation or protein expression level is not altered in expression, confirming that MMA sites contain regulated functions on their own. Collectively, we present a site-specific MMA dataset in human cells and demonstrate for the first time that MMA is a dynamic post-translational modification regulated during transcriptional arrest by a hitherto uncharacterized arginine demethylase.

U2 - 10.1074/mcp.O113.032748

DO - 10.1074/mcp.O113.032748

M3 - Journal article

C2 - 24563534

VL - 13

SP - 2072

EP - 2088

JO - Molecular and Cellular Proteomics

JF - Molecular and Cellular Proteomics

SN - 1535-9476

ER -

ID: 101063320