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Cited by 9Cancer-related gene regulationAdvanced Proteomics Techniques and ApplicationsRNA modifications and cancer

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ProMetheusDB: An In-Depth Analysis of the High-Quality Human Methyl-proteome

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Massignani, Enrico, Giambruno, Roberto, Maniaci, Marianna, Nicosia, Luciano, Yadav, Avinash, Cuomo, Alessandro, Raimondi, Francesco, Bonaldi, Tiziana·2022·Molecular & Cellular Proteomics
DOI 10.1016/j.mcpro.2022.100243PMC PMC9207298

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Abstract

Protein arginine (R) methylation is a post-translational modification involved in various biological processes, such as RNA splicing, DNA repair, immune response, signal transduction, and tumor development. Although several advancements were made in the study of this modification by mass spectrometry, researchers still face the problem of a high false discovery rate. We present a dataset of high-quality methylations obtained from several different heavy methyl stable isotope labeling with amino acids in cell culture experiments analyzed with a machine learning-based tool and show that this model allows for improved high-confidence identification of real methyl-peptides. Overall, our results are consistent with the notion that protein R methylation modulates protein-RNA interactions and suggest a role in rewiring protein-protein interactions, for which we provide experimental evidence for a representative case (i.e., NONO [non-POU domain-containing octamer-binding protein]-paraspeckle component 1 [PSPC1]). Upon intersecting our R-methyl-sites dataset with the PhosphoSitePlus phosphorylation dataset, we observed that R methylation correlates differently with S/T-Y phosphorylation in response to various stimuli. Finally, we explored the application of heavy methyl stable isotope labeling with amino acids in cell culture to identify unconventional methylated residues and successfully identified novel histone methylation marks on serine 28 and threonine 32 of H3. The database generated, named ProMetheusDB, is freely accessible at https://bioserver.ieo.it/shiny/app/prometheusdb.

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Metadata

Authors
Massignani, E., Giambruno, R., Maniaci, M., Nicosia, L., Yadav, A., Cuomo, A., Raimondi, F., & Bonaldi, T.
Affiliations
  • European School of Molecular Medicine (IT)
  • Italian Institute of Technology (IT)
  • European Institute of Oncology (IT)
  • Scuola Normale Superiore (IT)
  • University of Milan (IT)
Corresponding author
Bonaldi, Tiziana
ORCID
Venue
Molecular & Cellular Proteomics
Publisher
Elsevier BV
Published
2022-07
Volume
21
Issue
7
Pages
100243
ISSN
1535-9476 (ISSN-L)
DOI
10.1016/j.mcpro.2022.100243
PMC
PMC9207298
OpenAlex
W4280536202
Cited by
9
References
4
Citations by year
2026: 3 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 2
FWCI
0.49
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular & Cellular Proteomics (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, cc-by-nc-nd)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • Scuola Normale Superiore di Pisa (submittedVersion, cc-by-nc-nd)
Funders
  • Fondazione Italiana per la Ricerca sul Cancro (2018-22506)
  • Associazione Italiana per la Ricerca sul Cancro (2018-15741)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
Keywords
arginine methylation, methylome, machine learning, RNA-protein interactions, protein-protein interaction, NONO, PSPC1, phosphorylation, histone H3 methylation, post-translational modification
MeSH terms
Amino Acids, Humans, Isotope Labeling, Methylation, Protein Processing, Post-Translational, Mass Spectrometry, RNA-Binding Proteins, Proteome

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