Dataset Information

Non-Histone Arginine Methylation by Protein Arginine Methyltransferases.

ABSTRACT: Protein arginine methyltransferase (PRMT) enzymes play a crucial role in RNA splicing, DNA damage repair, cell signaling, and differentiation. Arginine methylation is a prominent posttransitional modification of histones and various non-histone proteins that can either activate or repress gene expression. The aberrant expression of PRMTs has been linked to multiple abnormalities, notably cancer. Herein, we review a number of non-histone protein substrates for all nine members of human PRMTs and how PRMT-mediated non-histone arginine methylation modulates various diseases. Additionally, we highlight the most recent clinical studies for several PRMT inhibitors.

SUBMITTER: Al-Hamashi AA

PROVIDER: S-EPMC7529871 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Non-Histone Arginine Methylation by Protein Arginine Methyltransferases.

Al-Hamashi Ayad A AA Diaz Krystal K Huang Rong R

Current protein & peptide science 20200101 7

Protein arginine methyltransferase (PRMT) enzymes play a crucial role in RNA splicing, DNA damage repair, cell signaling, and differentiation. Arginine methylation is a prominent posttransitional modification of histones and various non-histone proteins that can either activate or repress gene expression. The aberrant expression of PRMTs has been linked to multiple abnormalities, notably cancer. Herein, we review a number of non-histone protein substrates for all nine members of human PRMTs and ...[more]

PMID: 32379587

Similar Datasets

Project description:Heart failure remains a major cause of hospitalization and death worldwide. Heart failure can be caused by abnormalities in the epigenome resulting from dysregulation of histone-modifying enzymes. While chromatin enzymes catalyzing lysine acetylation and methylation of histones have been the topic of many investigations, the role of arginine methyltransferases has been overlooked. In an effort to understand regulatory mechanisms implicated in cardiac hypertrophy and heart failure, we assessed the expression of protein arginine methyltransferases (PRMTs) in the left ventricle of failing human hearts and control hearts. Our results show a significant up-regulation of protein arginine methyltransferase 6 (PRMT6) in failing human hearts compared to control hearts, which also occurs in the early phase of cardiac hypertrophy in mouse hearts subjected to pressure overload hypertrophy induced by trans-aortic constriction (TAC), and in neonatal rat ventricular myocytes (NRVM) stimulated with the hypertrophic agonist phenylephrine (PE). These changes are associated with a significant increase in arginine 2 asymmetric methylation of histone H3 (H3R2Me2a) and reduced lysine 4 tri-methylation of H3 (H3K4Me3) observed both in NRVM and in vivo. Importantly, forced expression of PRMT6 in NRVM enhances the expression of the hypertrophic marker, atrial natriuretic peptide (ANP). Conversely, specific silencing of PRMT6 reduces ANP protein expression and cell size, indicating that PRMT6 is critical for the PE-mediated hypertrophic response. Silencing of PRMT6 reduces H3R2Me2a, a mark normally associated with transcriptional repression. Furthermore, evaluation of cardiac contractility and global ion channel activity in live NRVM shows a striking reduction of spontaneous beating rates and prolongation of extra-cellular field potentials in cells expressing low-level PRMT6. Altogether, our results indicate that PRMT6 is a critical regulator of cardiac hypertrophy, implicating H3R2Me2a as an important histone modification. This study identifies PRMT6 as a new epigenetic regulator and suggests a new point of control in chromatin to inhibit pathological cardiac remodeling.

Dataset Information

Non-Histone Arginine Methylation by Protein Arginine Methyltransferases.

Publications

Non-Histone Arginine Methylation by Protein Arginine Methyltransferases.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets