Innate immunity to RNA virus is regulated by temporal and reversible sumoylation of RIG-I and MDA5

Related Experiment Video

Updated: Mar 7, 2026

Monitoring Activation of the Antiviral Pattern Recognition Receptors RIG-I And PKR By Limited Protease Digestion and Native PAGE
12:43

Monitoring Activation of the Antiviral Pattern Recognition Receptors RIG-I And PKR By Limited Protease Digestion and Native PAGE

Published on: July 29, 2014

12.7K

Ming-Ming Hu1, Chen-Yang Liao1, Qing Yang1

  • 1Medical Research Institute, Collaborative Innovation Center for Viral Immunology, School of Medicine, Wuhan University, Wuhan 430071, China.

The Journal of Experimental Medicine
|March 3, 2017
PubMed

Insights

TRIM38 regulates innate antiviral immunity by controlling the dynamic sumoylation of RIG-I and MDA5. This post-translational modification balances receptor stability and activation, ensuring an effective and timely antiviral response.

Area of Science:

  • Immunology
  • Molecular Biology
  • Virology

Background:

  • Cytosolic RNA sensors, RIG-I and MDA5, are crucial for innate antiviral immunity.
  • The dynamic regulation of RIG-I and MDA5 during antiviral responses remains unclear.

Purpose of the Study:

  • To investigate the role of TRIM38 in regulating MDA5 and RIG-I.
  • To elucidate the mechanisms controlling the dynamic modification and activity of MDA5 and RIG-I.

Main Methods:

  • Investigated TRIM38's function as a SUMO E3 ligase for MDA5 and RIG-I.
  • Analyzed sumoylation sites (K43/K865 for MDA5, K96/K888 for RIG-I).
  • Examined the impact of sumoylation on ubiquitination, degradation, dephosphorylation, and activation of MDA5 and RIG-I.

Main Results:

  • TRIM38 positively regulates MDA5- and RIG-I-mediated gene induction.
  • Sumoylation of MDA5 and RIG-I by TRIM38 suppresses their ubiquitination and degradation.
  • Sumoylation is essential for PP1-mediated dephosphorylation and activation of MDA5 and RIG-I.
  • SENP2-mediated desumoylation at late infection stages leads to MDA5 and RIG-I degradation.

Conclusions:

  • Dynamic sumoylation and desumoylation of MDA5 and RIG-I are critical for effective RNA virus innate immunity.
  • This regulatory mechanism ensures both efficient viral clearance and timely termination of the immune response.

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