Dataset Information

The protein arginine methyltransferase PRMT9 attenuates MAVS activation through arginine methylation.

ABSTRACT: The signaling adaptor MAVS forms prion-like aggregates to activate the innate antiviral immune response after viral infection. However, spontaneous aggregation of MAVS can lead to autoimmune diseases. The molecular mechanism that prevents MAVS from spontaneous aggregation in resting cells has been enigmatic. Here we report that protein arginine methyltransferase 9 targets MAVS directly and catalyzes the arginine methylation of MAVS at the Arg41 and Arg43. In the resting state, this modification inhibits MAVS aggregation and autoactivation of MAVS. Upon virus infection, PRMT9 dissociates from the mitochondria, leading to the aggregation and activation of MAVS. Our study implicates a form of post-translational modification on MAVS, which can keep MAVS inactive in physiological conditions to maintain innate immune homeostasis.

SUBMITTER: Bai X

PROVIDER: S-EPMC9418238 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The protein arginine methyltransferase PRMT9 attenuates MAVS activation through arginine methylation.

Bai Xuemei X Sui Chao C Liu Feng F Chen Tian T Zhang Lei L Zheng Yi Y Liu Bingyu B Gao Chengjiang C

Nature communications 20220826 1

The signaling adaptor MAVS forms prion-like aggregates to activate the innate antiviral immune response after viral infection. However, spontaneous aggregation of MAVS can lead to autoimmune diseases. The molecular mechanism that prevents MAVS from spontaneous aggregation in resting cells has been enigmatic. Here we report that protein arginine methyltransferase 9 targets MAVS directly and catalyzes the arginine methylation of MAVS at the Arg41 and Arg43. In the resting state, this modification ...[more]

PMID: 36028484

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

The protein arginine methyltransferase PRMT9 attenuates MAVS activation through arginine methylation.

Publications

The protein arginine methyltransferase PRMT9 attenuates MAVS activation through arginine methylation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets