FAM76B regulates NF-κB-mediated inflammatory pathway by influencing the translocation of hnRNPA2B1
- Shaanxi Normal University, China
- University of Utah, United States
Abstract
FAM76B has been reported to be a nuclear speckle localized protein with unknown function. In this study, FAM76B was first demonstrated to inhibit the NF-κB-mediated inflammatory pathway by affecting the translocation of hnRNPA2B1 in vitro. We further showed that FAM76B suppressed inflammation in vivo using a traumatic brain injury (TBI) mouse model. Lastly, FAM76B was shown to interact with hnRNPA2B1 in human tissues taken from patients with acute, organizing, and chronic TBI, and with different neurodegenerative diseases. The results suggested that FAM76B mediated neuroinflammation via influencing the translocation of hnRNPA2B1in vivo during TBI repair and neurodegenerative diseases. In summary, we for the first time demonstrated the role of FAM76B in regulating inflammation and further showed that FAM76B could regulate the NF-κB-mediated inflammatory pathway by affecting hnRNPA2B1 translocation, which provides new information for studying the mechanism of inflammation regulation.
Data availability
The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the iProX partner repository [1] with the dataset identifier PXD037539. ([1] Ma J, et al. (2019) iProX: an integrated proteome resource. Nucleic Acids Res, 47, D1211-D1217).
Article and author information
Author details
Funding
The national natrual science foundation of China (81773265)
- Haibin Xia
Key Research and Development Plan of Shaanxi Province (2018SF-106)
- Haibin Xia
the natrual science foundation of Shaanxi Province (2023-JC-YB-642)
- Xiaojing Zheng
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal studies were performed in accordance with institutional guidelines and with approval by the Institutional Animal Care and Use Committee of Shaanxi Normal University (SNNU 2019-0128). Ethical permit of the use of the samples of human brain autopsy specimens was granted by the ethics committee of Shaanxi Normal University (SNNU 2019-0026).
Copyright
© 2023, Wang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 492
- views
-
- 93
- downloads
-
- 2
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
FAM76B regulates NF-κB-mediated inflammatory pathway by influencing the translocation of hnRNPA2B1
eLife 12:e85659.
https://doi.org/10.7554/eLife.85659
Further reading
-
- Cell Biology
- Microbiology and Infectious Disease
Zika virus (ZIKV) infection causes significant human disease that, with no approved treatment or vaccine, constitutes a major public health concern. Its life cycle entirely relies on the cytoplasmic fate of the viral RNA genome (vRNA) through a fine-tuned equilibrium between vRNA translation, replication, and packaging into new virions, all within virus-induced replication organelles (vROs). In this study, with an RNA interference (RNAi) mini-screening and subsequent functional characterization, we have identified insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) as a new host dependency factor that regulates vRNA synthesis. In infected cells, IGF2BP2 associates with viral NS5 polymerase and redistributes to the perinuclear viral replication compartment. Combined fluorescence in situ hybridization-based confocal imaging, in vitro binding assays, and immunoprecipitation coupled to RT-qPCR showed that IGF2BP2 directly interacts with ZIKV vRNA 3’ nontranslated region. Using ZIKV sub-genomic replicons and a replication-independent vRO induction system, we demonstrated that IGF2BP2 knockdown impairs de novo vRO biogenesis and, consistently, vRNA synthesis. Finally, the analysis of immunopurified IGF2BP2 complex using quantitative mass spectrometry and RT-qPCR revealed that ZIKV infection alters the protein and RNA interactomes of IGF2BP2. Altogether, our data support that ZIKV hijacks and remodels the IGF2BP2 ribonucleoprotein complex to regulate vRO biogenesis and vRNA neosynthesis.
-
- Cell Biology
A reciprocal interaction between gut bacteria and gut cells affects protein absorption in the host.
