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Abstract
Arginine methylation (ArgMe) is a post-translational modification that consists on the addition of methyl groups to the target Arg in proteins. Recent studies have identified hundreds of proteins undergoing ArgMe in tissues such as brain. However, only a handful of non-histone proteins are known to undergo ArgMe in the heart.
Rationale Ongoing research within the group has suggested that proteins involved in glycolysis are more likely to undergo ArgMe. Here, we decided to 1) identify cardiac proteins undergoing ArgMe, and 2) uncover the relevance of ArgMe in cardiac disease, with a focus on high glucose-induced cardiac hypertrophy.
Methodology We used a combination of big data analysis, and experimental approaches. We searched public proteomics data for cardiac protein ArgMe. We used H9c2 cardiac-like cells to study ArgMe profiles under glucose-induced cell hypertrophy.
Results We identified 104 ArgMe sites in 59 non-histone cardiac proteins which are conserved in human fetal and adult heart. We found enrichment of Gene Ontology (GO) terms related to cardiomyocyte contraction in our subset of methylated proteins. There was a disease-causing (often hypertrophic cardiomyopathy) or predicted damaging mutation reported at the would-have-been methylated Arg in 50 of the 104 ArgMe sites. We induced H9c2 cell hypertrophy using 30 mM glucose and found that protein ArgMe profiles significantly changed after 72 h.
Conclusion We identified the “arginine methylome” of human heart, and provided evidence that ArgMe could play important, but currently unexplored, roles in cardiac disease, including high glucose-induced cardiac hypertrophy.