TRIM41, a tripartite motif-containing ubiquitin E3 ligase, plays crucial roles in multiple biological processes. It is involved in innate antiviral responses, immune regulation, and cellular protein homeostasis. Through ubiquitination, it targets specific proteins for degradation, thus regulating key pathways such as those related to viral infection, meiosis, and cellular stress responses [1-10]. Genetic models, especially knockout mouse models, are valuable tools for studying its functions.

In male mice, Trim41 knockout leads to synaptonemal complex protein 3 (SYCP3) overloading on the X chromosome, indicating its essential role in regulating chromosome axis protein dynamics and proper meiotic progression [1]. In antiviral defense, TRIM41 deficiency impairs the production of inflammatory cytokines and type I interferons in macrophages after nucleic acid-mimic transfection and virus infection. In vivo, it results in an impaired innate response against viruses. Mechanistically, TRIM41 polyubiquitinates BCL10 and recruits NEMO to activate NF-κB and TBK1-IRF3 pathways [2]. In nasopharyngeal carcinoma, circRNA_0067717 acts as a scaffold for TRIM41 and p53, promoting TRIM41-induced p53 ubiquitination and degradation, which enhances paclitaxel chemoresistance [3].

In conclusion, TRIM41 is a vital E3 ubiquitin ligase involved in diverse biological functions, including meiosis and antiviral responses. The use of KO mouse models has significantly contributed to understanding its role in these processes, providing insights into potential therapeutic targets for diseases related to meiotic disorders and viral infections.

References:

1. Oura, Seiya, Hino, Toshiaki, Satoh, Takashi, Ishiguro, Kei-Ichiro, Ikawa, Masahito. 2022. Trim41 is required to regulate chromosome axis protein dynamics and meiosis in male mice. In PLoS genetics, 18, e1010241. doi:10.1371/journal.pgen.1010241. https://pubmed.ncbi.nlm.nih.gov/35648791/

2. Yu, Zhou, Li, Xuelian, Yang, Mingjin, Chen, Taoyong, Cao, Xuetao. 2021. TRIM41 is required to innate antiviral response by polyubiquitinating BCL10 and recruiting NEMO. In Signal transduction and targeted therapy, 6, 90. doi:10.1038/s41392-021-00477-8. https://pubmed.ncbi.nlm.nih.gov/33640899/

3. Cheng, Yaxin, Zhu, Yuxing, Xiao, Mengqing, Chen, Haotian, Cao, Ke. 2023. circRNA_0067717 promotes paclitaxel resistance in nasopharyngeal carcinoma by acting as a scaffold for TRIM41 and p53. In Cellular oncology (Dordrecht, Netherlands), 46, 677-695. doi:10.1007/s13402-023-00776-y. https://pubmed.ncbi.nlm.nih.gov/36705889/