Dataset Information

Global analysis of protein arginine methylation.

ABSTRACT: Quantitative information about the levels and dynamics of post-translational modifications (PTMs) is critical for an understanding of cellular functions. Protein arginine methylation (ArgMet) is an important subclass of PTMs and is involved in a plethora of (patho)physiological processes. However, because of the lack of methods for global analysis of ArgMet, the link between ArgMet levels, dynamics, and (patho)physiology remains largely unknown. We utilized the high sensitivity and robustness of nuclear magnetic resonance (NMR) spectroscopy to develop a general method for the quantification of global protein ArgMet. Our NMR-based approach enables the detection of protein ArgMet in purified proteins, cells, organoids, and mouse tissues. We demonstrate that the process of ArgMet is a highly prevalent PTM and can be modulated by small-molecule inhibitors and metabolites and changes in cancer and during aging. Thus, our approach enables us to address a wide range of biological questions related to ArgMet in health and disease.

SUBMITTER: Zhang F

PROVIDER: S-EPMC9017121 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Global analysis of protein arginine methylation.

Zhang Fangrong F Kerbl-Knapp Jakob J Rodriguez Colman Maria J MJ Meinitzer Andreas A Macher Therese T Vujić Nemanja N Fasching Sandra S Jany-Luig Evelyne E Korbelius Melanie M Kuentzel Katharina B KB Mack Maximilian M Akhmetshina Alena A Pirchheim Anita A Paar Margret M Rinner Beate B Hörl Gerd G Steyrer Ernst E Stelzl Ulrich U Burgering Boudewijn B Eisenberg Tobias T Pertschy Brigitte B Kratky Dagmar D Madl Tobias T

Cell reports methods 20210621 2

Quantitative information about the levels and dynamics of post-translational modifications (PTMs) is critical for an understanding of cellular functions. Protein arginine methylation (ArgMet) is an important subclass of PTMs and is involved in a plethora of (patho)physiological processes. However, because of the lack of methods for global analysis of ArgMet, the link between ArgMet levels, dynamics, and (patho)physiology remains largely unknown. We utilized the high sensitivity and robustness of ...[more]

PMID: 35475236

Similar Datasets

Project description:Arginine methylation is a common posttranslational modification with reported functions in transcription, RNA processing and translation, and DNA repair. Trypanosomes encode five protein arginine methyltransferases, suggesting that arginine methylation exerts widespread impacts on the biology of these organisms. Here, we performed a global proteomic analysis of Trypanosoma brucei to identify arginine methylated proteins and their sites of modification. Using an approach entailing two-dimensional chromatographic separation and alternating electron transfer dissociation and collision induced dissociation, we identified 1332 methylarginines in 676 proteins. The resulting data set represents the largest compilation of arginine methylated proteins in any organism to date. Functional classification revealed numerous arginine methylated proteins involved in flagellar function, RNA metabolism, DNA replication and repair, and intracellular protein trafficking. Thus, arginine methylation has the potential to impact aspects of T. brucei gene expression, cell biology, and pathogenesis. Interestingly, pathways with known methylated proteins in higher eukaryotes were identified in this study, but often different components of the pathway were methylated in trypanosomes. Methylarginines were often identified in glycine rich contexts, although exceptions to this rule were detected. Collectively, these data inform on a multitude of aspects of trypanosome biology and serve as a guide for the identification of homologous arginine methylated proteins in higher eukaryotes.T. brucei is a protozoan parasite that causes lethal African sleeping sickness in humans and nagana in livestock, thereby imposing a significant medical and economic burden on sub-Saharan Africa. The parasite encounters very different environments as it cycles between mammalian and insect hosts, and must exert cellular responses to these varying milieus. One mechanism by which all cells respond to changing environments is through posttranslational modification of proteins. Arginine methylation is one such modification that can dramatically impact protein-protein and protein-nucleic acid interactions and subcellular localization of proteins. To define the breadth of arginine methylation in trypanosomes and identify target proteins, we performed a global proteomic analysis of arginine methylated proteins in insect stage T. brucei. We identified 1332 methylarginines in 676 proteins, generating the largest compilation of methylarginine containing proteins in any organism to date. Numerous arginine methylated proteins function in RNA and DNA related processes, suggesting this modification can impact T. brucei genome integrity and gene regulation at numerous points. Other processes that appear to be strongly influenced by arginine methylation are intracellular protein trafficking, signaling, protein folding and degradation, and flagellar function. The widespread nature of arginine methylation in trypanosomes highlights its potential to greatly affect parasite biology and pathogenesis.

Dataset Information

Global analysis of protein arginine methylation.

Publications

Global analysis of protein arginine methylation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets