Bibliographic Details
| Title: |
Grass Carp Mex3A Promotes Ubiquitination and Degradation of RIG-I to Inhibit Innate Immune Response |
| Authors: |
Zeyin Jiang, Zhichao Sun, Jihuan Hu, Dongming Li, Xiaowen Xu, Meifeng Li, Zhiqing Feng, Shanshan Zeng, Huiling Mao, Chengyu Hu |
| Source: |
Frontiers in Immunology, Vol 13 (2022) |
| Publisher Information: |
Frontiers Media S.A., 2022. |
| Publication Year: |
2022 |
| Collection: |
LCC:Immunologic diseases. Allergy |
| Subject Terms: |
Mex3A, RIG-I, negative regulator, ubiquitination, fish, Immunologic diseases. Allergy, RC581-607 |
| More Details: |
As one of the Mex3 family members, Mex3A is crucial in cell proliferation, migration, and apoptosis in mammals. In this study, a novel gene homologous to mammalian Mex3A (named CiMex3A, MW368974) was cloned and identified in grass carp, which is 1,521 bp in length encoding a putative polypeptide of 506 amino acids. In CIK cells, CiMex3A is upregulated after stimulation with LPS, Z-DNA, and especially with intracellular poly(I:C). CiMex3A overexpression reduces the expressions of IFN1, ISG15, and pro-inflammatory factors IL8 and TNFα; likewise, Mex3A inhibits IRF3 phosphorylation upon treatment with poly(I:C). A screening test to identify potential targets suggested that CiMex3A interacts with RIG-I exclusively. Co-localization analysis showed that Mex3A and RIG-I are simultaneously located in the endoplasmic reticulum, while they rarely appear in the endosome, mitochondria, or lysosome after exposure to poly(I:C). However, RIG-I is mainly located in the early endosome and then transferred to the late endosome following stimulation with poly(I:C). Moreover, we investigated the molecular mechanism underlying CiMex3A-mediated suppression of RIG-I ubiquitination. The results demonstrated that Mex3A truncation mutant (deletion in the RING domain) can still interact physically with RIG-I, but fail to degrade it, suggesting that Mex3A also acts as a RING-type E3 ubiquitin ligase. Taken together, this study showed that grass carp Mex3A can interact with RIG-I in the endoplasmic reticulum following poly(I:C) stimulation, and then Mex3A facilitates the ubiquitination and degradation of RIG-I to inhibit IRF3-mediated innate antiviral immune response. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1664-3224 |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fimmu.2022.909315/full; https://doaj.org/toc/1664-3224 |
| DOI: |
10.3389/fimmu.2022.909315 |
| Access URL: |
https://doaj.org/article/c8c7c1f064444cc1a8208bffb1d32987 |
| Accession Number: |
edsdoj.8c7c1f064444cc1a8208bffb1d32987 |
| Database: |
Directory of Open Access Journals |
