Proteome-wide analysis of arginine monomethylation reveals widespread occurrence in human cells

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Proteome-wide analysis of arginine monomethylation reveals widespread occurrence in human cells. / Larsen, Sara C; Sylvestersen, Kathrine B; Mund, Andreas; Lyon, David; Mullari, Meeli; Madsen, Maria V; Daniel, Jeremy A; Jensen, Lars J; Nielsen, Michael Lund.

In: Science Signaling, Vol. 9, No. 443, rs9, 30.08.2016.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Larsen, SC, Sylvestersen, KB, Mund, A, Lyon, D, Mullari, M, Madsen, MV, Daniel, JA, Jensen, LJ & Nielsen, ML 2016, 'Proteome-wide analysis of arginine monomethylation reveals widespread occurrence in human cells', Science Signaling, vol. 9, no. 443, rs9. https://doi.org/10.1126/scisignal.aaf7329

APA

Larsen, S. C., Sylvestersen, K. B., Mund, A., Lyon, D., Mullari, M., Madsen, M. V., Daniel, J. A., Jensen, L. J., & Nielsen, M. L. (2016). Proteome-wide analysis of arginine monomethylation reveals widespread occurrence in human cells. Science Signaling, 9(443), [rs9]. https://doi.org/10.1126/scisignal.aaf7329

Vancouver

Larsen SC, Sylvestersen KB, Mund A, Lyon D, Mullari M, Madsen MV et al. Proteome-wide analysis of arginine monomethylation reveals widespread occurrence in human cells. Science Signaling. 2016 Aug 30;9(443). rs9. https://doi.org/10.1126/scisignal.aaf7329

Author

Larsen, Sara C ; Sylvestersen, Kathrine B ; Mund, Andreas ; Lyon, David ; Mullari, Meeli ; Madsen, Maria V ; Daniel, Jeremy A ; Jensen, Lars J ; Nielsen, Michael Lund. / Proteome-wide analysis of arginine monomethylation reveals widespread occurrence in human cells. In: Science Signaling. 2016 ; Vol. 9, No. 443.

Bibtex

@article{f08c338d23ef4f3a8def9c0b5f16d893,
title = "Proteome-wide analysis of arginine monomethylation reveals widespread occurrence in human cells",
abstract = "The posttranslational modification of proteins by arginine methylation is functionally important, yet the breadth of this modification is not well characterized. Using high-resolution mass spectrometry, we identified 8030 arginine methylation sites within 3300 human proteins in human embryonic kidney 293 cells, indicating that the occurrence of this modification is comparable to phosphorylation and ubiquitylation. A site-level conservation analysis revealed that arginine methylation sites are less evolutionarily conserved compared to arginines that were not identified as modified by methylation. Through quantitative proteomics and RNA interference to examine arginine methylation stoichiometry, we unexpectedly found that the protein arginine methyltransferase (PRMT) family of arginine methyltransferases catalyzed methylation independently of arginine sequence context. In contrast to the frequency of somatic mutations at arginine methylation sites throughout the proteome, we observed that somatic mutations were common at arginine methylation sites in proteins involved in mRNA splicing. Furthermore, in HeLa and U2OS cells, we found that distinct arginine methyltransferases differentially regulated the functions of the pre-mRNA splicing factor SRSF2 (serine/arginine-rich splicing factor 2) and the RNA transport ribonucleoprotein HNRNPUL1 (heterogeneous nuclear ribonucleoprotein U-like 1). Knocking down PRMT5 impaired the RNA binding function of SRSF2, whereas knocking down PRMT4 [also known as coactivator-associated arginine methyltransferase 1 (CARM1)] or PRMT1 increased the RNA binding function of HNRNPUL1. High-content single-cell imaging additionally revealed that knocking down CARM1 promoted the nuclear accumulation of SRSF2, independent of cell cycle phase. Collectively, the presented human arginine methylome provides a missing piece in the global and integrative view of cellular physiology and protein regulation.",
keywords = "Journal Article",
author = "Larsen, {Sara C} and Sylvestersen, {Kathrine B} and Andreas Mund and David Lyon and Meeli Mullari and Madsen, {Maria V} and Daniel, {Jeremy A} and Jensen, {Lars J} and Nielsen, {Michael Lund}",
note = "Copyright {\textcopyright} 2016, American Association for the Advancement of Science.",
year = "2016",
month = aug,
day = "30",
doi = "10.1126/scisignal.aaf7329",
language = "English",
volume = "9",
journal = "Science Signaling",
issn = "1945-0877",
publisher = "American Association for the Advancement of Science",
number = "443",

}

RIS

TY - JOUR

T1 - Proteome-wide analysis of arginine monomethylation reveals widespread occurrence in human cells

AU - Larsen, Sara C

AU - Sylvestersen, Kathrine B

AU - Mund, Andreas

AU - Lyon, David

AU - Mullari, Meeli

AU - Madsen, Maria V

AU - Daniel, Jeremy A

AU - Jensen, Lars J

AU - Nielsen, Michael Lund

N1 - Copyright © 2016, American Association for the Advancement of Science.

PY - 2016/8/30

Y1 - 2016/8/30

N2 - The posttranslational modification of proteins by arginine methylation is functionally important, yet the breadth of this modification is not well characterized. Using high-resolution mass spectrometry, we identified 8030 arginine methylation sites within 3300 human proteins in human embryonic kidney 293 cells, indicating that the occurrence of this modification is comparable to phosphorylation and ubiquitylation. A site-level conservation analysis revealed that arginine methylation sites are less evolutionarily conserved compared to arginines that were not identified as modified by methylation. Through quantitative proteomics and RNA interference to examine arginine methylation stoichiometry, we unexpectedly found that the protein arginine methyltransferase (PRMT) family of arginine methyltransferases catalyzed methylation independently of arginine sequence context. In contrast to the frequency of somatic mutations at arginine methylation sites throughout the proteome, we observed that somatic mutations were common at arginine methylation sites in proteins involved in mRNA splicing. Furthermore, in HeLa and U2OS cells, we found that distinct arginine methyltransferases differentially regulated the functions of the pre-mRNA splicing factor SRSF2 (serine/arginine-rich splicing factor 2) and the RNA transport ribonucleoprotein HNRNPUL1 (heterogeneous nuclear ribonucleoprotein U-like 1). Knocking down PRMT5 impaired the RNA binding function of SRSF2, whereas knocking down PRMT4 [also known as coactivator-associated arginine methyltransferase 1 (CARM1)] or PRMT1 increased the RNA binding function of HNRNPUL1. High-content single-cell imaging additionally revealed that knocking down CARM1 promoted the nuclear accumulation of SRSF2, independent of cell cycle phase. Collectively, the presented human arginine methylome provides a missing piece in the global and integrative view of cellular physiology and protein regulation.

AB - The posttranslational modification of proteins by arginine methylation is functionally important, yet the breadth of this modification is not well characterized. Using high-resolution mass spectrometry, we identified 8030 arginine methylation sites within 3300 human proteins in human embryonic kidney 293 cells, indicating that the occurrence of this modification is comparable to phosphorylation and ubiquitylation. A site-level conservation analysis revealed that arginine methylation sites are less evolutionarily conserved compared to arginines that were not identified as modified by methylation. Through quantitative proteomics and RNA interference to examine arginine methylation stoichiometry, we unexpectedly found that the protein arginine methyltransferase (PRMT) family of arginine methyltransferases catalyzed methylation independently of arginine sequence context. In contrast to the frequency of somatic mutations at arginine methylation sites throughout the proteome, we observed that somatic mutations were common at arginine methylation sites in proteins involved in mRNA splicing. Furthermore, in HeLa and U2OS cells, we found that distinct arginine methyltransferases differentially regulated the functions of the pre-mRNA splicing factor SRSF2 (serine/arginine-rich splicing factor 2) and the RNA transport ribonucleoprotein HNRNPUL1 (heterogeneous nuclear ribonucleoprotein U-like 1). Knocking down PRMT5 impaired the RNA binding function of SRSF2, whereas knocking down PRMT4 [also known as coactivator-associated arginine methyltransferase 1 (CARM1)] or PRMT1 increased the RNA binding function of HNRNPUL1. High-content single-cell imaging additionally revealed that knocking down CARM1 promoted the nuclear accumulation of SRSF2, independent of cell cycle phase. Collectively, the presented human arginine methylome provides a missing piece in the global and integrative view of cellular physiology and protein regulation.

KW - Journal Article

U2 - 10.1126/scisignal.aaf7329

DO - 10.1126/scisignal.aaf7329

M3 - Journal article

C2 - 27577262

VL - 9

JO - Science Signaling

JF - Science Signaling

SN - 1945-0877

IS - 443

M1 - rs9

ER -

ID: 165178924