TRIM7, also known as RNF90, is an E3 ubiquitin ligase. It plays significant roles in various biological processes, mainly in promoting host defense against viral infections, regulating immune signaling pathways, autophagy, and ferroptosis [1,2,3]. It is involved in pathways like the IFN-β signaling pathway and is crucial for maintaining the balance of the body's defense mechanisms and cellular homeostasis. Genetic models, especially KO mouse models, are valuable for studying its functions.

In Trim7 -/- mice, there are increased pathology and virus titers associated with epithelial apoptosis and dysregulated immune responses when infected with SARS-CoV-2, indicating that TRIM7 limits apoptosis and viral replication by ubiquitinating the viral membrane protein [4,5]. In L. monocytogenes infection, TRIM7 deficiency in mice or cells results in elevated innate immune responses and increased infection, as it positively regulates autophagosome accumulation by promoting the ubiquitination of ATG7 [2]. In glioblastoma cells, TRIM7 deletion sensitizes cells to temozolomide therapy, and its absence leads to increased iron accumulation, lipid peroxidation, and ferroptosis [3].

In conclusion, TRIM7 is essential in host-pathogen interactions, autophagy, and ferroptosis. The use of KO mouse models has revealed its significance in viral diseases like COVID-19, intracellular bacterial infections such as L. monocytogenes, and in glioblastoma. These findings provide a basis for understanding the underlying mechanisms of these diseases and developing potential therapeutic strategies.

References:

1. Liu, Yiyang, Jiang, Lu, Sun, Xuemeng, Liu, Yihan, Zhang, Leiliang. 2023. Interplay between TRIM7 and antiviral immunity. In Frontiers in cellular and infection microbiology, 13, 1256882. doi:10.3389/fcimb.2023.1256882. https://pubmed.ncbi.nlm.nih.gov/37719674/

2. Wang, Jie, Qin, Xiao, Huang, Yulu, Wang, Hui, Yang, Bo. 2023. TRIM7/RNF90 promotes autophagy via regulation of ATG7 ubiquitination during L. monocytogenes infection. In Autophagy, 19, 1844-1862. doi:10.1080/15548627.2022.2162706. https://pubmed.ncbi.nlm.nih.gov/36576150/

3. Li, Kaiqiang, Chen, Bingyu, Xu, Aibo, Ge, Feihang, Wang, Zhen. 2022. TRIM7 modulates NCOA4-mediated ferritinophagy and ferroptosis in glioblastoma cells. In Redox biology, 56, 102451. doi:10.1016/j.redox.2022.102451. https://pubmed.ncbi.nlm.nih.gov/36067704/

4. Gonzalez-Orozco, Maria, Tseng, Hsiang-Chi, Hage, Adam, Freiberg, Alexander N, Rajsbaum, Ricardo. 2024. TRIM7 ubiquitinates SARS-CoV-2 membrane protein to limit apoptosis and viral replication. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.06.17.599107. https://pubmed.ncbi.nlm.nih.gov/38948778/

5. Gonzalez-Orozco, Maria, Tseng, Hsiang-Chi, Hage, Adam, Freiberg, Alexander N, Rajsbaum, Ricardo. 2024. TRIM7 ubiquitinates SARS-CoV-2 membrane protein to limit apoptosis and viral replication. In Nature communications, 15, 10438. doi:10.1038/s41467-024-54762-5. https://pubmed.ncbi.nlm.nih.gov/39616206/