ISG20, also known as HEM45 (HeLa estrogen-modulated, band 45), is an interferon-stimulated exonuclease gene that codes for a 20-kDa protein. It belongs to the DEDD exonucleases family and has RNase properties, capable of cleaving single-stranded RNA and DNA. ISG20 plays a crucial role in interferon-mediated antiviral activities and may also be related to some inflammatory conditions and cancer-related processes [3].

ISG20 inhibits the replication of various viruses. For example, overexpression of ovine ISG20 (oISG20) suppresses bluetongue virus (BTV) replication, while its knockdown increases viral replication. oISG20 co-localizes with BTV proteins and directly interacts with VP4, and its exonuclease activity is essential for BTV replication inhibition [1]. In the context of acute kidney injury (AKI), tubule-specific deficiency of ISG20 in mice significantly aggravates renal injury and RNA oxidation, suggesting ISG20's role in restricting RNA oxidation in an exoribonuclease activity-dependent manner [2]. In clear cell renal cell carcinoma (ccRCC), knockdown of ISG20 expression inhibits cell growth, migration, and invasion, indicating its role in promoting ccRCC progression [4].

In summary, ISG20 is an important gene involved in antiviral defense, RNA oxidation regulation in AKI, and tumor-related processes such as in ccRCC. The use of gene knockout or knockdown models in mice and cell lines has revealed its diverse functions in different biological processes and disease conditions, providing potential targets for antiviral and cancer therapies.

References:

1. Kang, Di, Gao, Shandian, Tian, Zhancheng, Du, Junzheng, Yin, Hong. 2022. ISG20 inhibits bluetongue virus replication. In Virologica Sinica, 37, 521-530. doi:10.1016/j.virs.2022.04.010. https://pubmed.ncbi.nlm.nih.gov/35513266/

2. Jia, Meng, Li, Liang, Chen, Ruiqi, Tang, Wei, Yi, Fan. 2023. Targeting RNA oxidation by ISG20-mediated degradation is a potential therapeutic strategy for acute kidney injury. In Molecular therapy : the journal of the American Society of Gene Therapy, 31, 3034-3051. doi:10.1016/j.ymthe.2023.07.008. https://pubmed.ncbi.nlm.nih.gov/37452495/

3. Zheng, Zhiwei, Wang, Lin, Pan, Jihong. . Interferon-stimulated gene 20-kDa protein (ISG20) in infection and disease: Review and outlook. In Intractable & rare diseases research, 6, 35-40. doi:10.5582/irdr.2017.01004. https://pubmed.ncbi.nlm.nih.gov/28357179/

4. Xu, Tianbo, Ruan, Hailong, Gao, Su, Chen, Ke, Zhang, Xiaoping. 2020. ISG20 serves as a potential biomarker and drives tumor progression in clear cell renal cell carcinoma. In Aging, 12, 1808-1827. doi:10.18632/aging.102714. https://pubmed.ncbi.nlm.nih.gov/32003757/