2. Academic Validation
  3. The Zinc-Finger Protein ZCCHC3 Binds RNA and Facilitates Viral RNA Sensing and Activation of the RIG-I-like Receptors

The Zinc-Finger Protein ZCCHC3 Binds RNA and Facilitates Viral RNA Sensing and Activation of the RIG-I-like Receptors

  • Immunity. 2018 Sep 18;49(3):438-448.e5. doi: 10.1016/j.immuni.2018.08.014.
Huan Lian 1,  Ru Zang 1,  Jin Wei 1,  Wen Ye 1,  Ming-Ming Hu 1,  Yun-Da Chen 2,  Xia-Nan Zhang 2,  Yi Guo 2,  Cao-Qi Lei 2,  Qing Yang 1,  Wei-Wei Luo 3,  Shu Li 4,  Hong-Bing Shu 5
Affiliations

Affiliations

  • 1 Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China.
  • 2 Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China; College of Life Sciences, Wuhan University, Wuhan 430072, China.
  • 3 Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
  • 4 Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China. Electronic address: [email protected].
  • 5 Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China; College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: [email protected].
PMID: 30193849 DOI: 10.1016/j.immuni.2018.08.014
Abstract

Recognition of viral RNA by the retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) initiates innate Antiviral immune response. How the binding of viral RNA to and activation of the RLRs are regulated remains enigmatic. In this study, we identified ZCCHC3 as a positive regulator of the RLRs including RIG-I and MDA5. ZCCHC3 deficiency markedly inhibited RNA virus-triggered induction of downstream Antiviral genes, and ZCCHC3-deficient mice were more susceptible to RNA virus Infection. ZCCHC3 was associated with RIG-I and MDA5 and functions in two distinct processes for regulation of RIG-I and MDA5 activities. ZCCHC3 bound to dsRNA and enhanced the binding of RIG-I and MDA5 to dsRNA. ZCCHC3 also recruited the E3 ubiquitin ligase TRIM25 to the RIG-I and MDA5 complexes to facilitate its K63-linked polyubiquitination and activation. Thus, ZCCHC3 is a co-receptor for RIG-I and MDA5, which is critical for RLR-mediated innate immune response to RNA virus.

Keywords

RIG-I-like receptors; RNA virus; ZCCHC3; co-receptor; innate antiviral response; polyubiquitination.

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