Mapping arginine methylation in the human body and cardiac disease

Onwuli, Donatus O.; Rigau-Roca, Laura; Cawthorne, Chris; Beltran-Alvarez, Pedro

Abstract

Purpose Arginine methylation (ArgMe) is one of the most ubiquitous post-translational modifications, and hundreds of proteins undergo ArgMe in e.g. brain. However, the scope of ArgMe in many tissues, including the heart, is currently under explored. Here, we aimed to 1) identify proteins undergoing ArgMe in human organs, and 2) expose the relevance of ArgMe in cardiac disease. Experimental design We used publicly available proteomic data to search for ArgMe in 13 human tissues. We used glucose to induce H9c2 cardiac-like cell hypertrophy. Results Our results show that ArgMe is mainly tissue-specific; nevertheless, we suggest an embryonic origin of core ArgMe events. In the heart, we found 103 mostly novel ArgMe sites in 58 non-histone proteins. We provide compelling evidence that cardiac protein ArgMe is relevant to cardiomyocyte ontology, and important for proper cardiac function. This is highlighted by the fact that genetic mutations affecting methylated arginine positions are often associated with cardiac disease, including hypertrophic cardiomyopathy. We provide pilot experimental data suggesting significant changes in ArgMe profiles of H9c2 cells upon induction of cell hypertrophy using glucose. Conclusions and clinical relevance Our work calls for in-depth investigation of ArgMe in normal and diseased tissues, using methods including clinical proteomics.

Citation

Onwuli, D. O., Rigau-Roca, L., Cawthorne, C., & Beltran-Alvarez, P. (2017). Mapping arginine methylation in the human body and cardiac disease. Proteomics. Clinical applications, 11(1-2), Article ARTN 1600106. https://doi.org/10.1002/prca.201600106

• Journal Article Type: Article
• Acceptance Date: Sep 2, 2016
• Online Publication Date: Nov 25, 2016
• Publication Date: 2017-01
• Deposit Date: Sep 13, 2016
• Publicly Available Date: Nov 25, 2016
• Journal: Proteomics : clinical applications
• Print ISSN: 1862-8346
• Publisher: Wiley-VCH Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 1-2
• Article Number: ARTN 1600106
• DOI: https://doi.org/10.1002/prca.201600106
• Keywords: Clinical Biochemistry
• Public URL: https://hull-repository.worktribe.com/output/442935
• Publisher URL: http://onlinelibrary.wiley.com/doi/10.1002/prca.201600106/abstract
• Additional Information: Authors' accepted manuscript of article: Onwuli, D. O., Rigau-Roca, L., Cawthorne, C. and Beltran-Alvarez, P. (2017), Mapping arginine methylation in the human body and cardiac disease. Prot. Clin. Appl., 11: issue 1-2, 1600106, which has been published in final form at http://dx.doi.org/10.1002/prca.201600106
• Contract Date: Sep 13, 2016