ISG20 gene

The ISG20 gene (ISG20 stands for: Interferon Stimulated Exonuclease Gene 20) is a protein-coding gene located on chromosome 15q26.1. Activities associated with this gene include nucleic acid binding and 3'-5' RNA exonuclease activity. Associated pathways include cytokine signaling in the immune system and antiviral activities through IFN-stimulated genes. An important paralog of this gene is AEN.

The protein encoded by the ISG20 gene is an interferon-induced antiviral exoribonuclease that acts mainly on single-stranded RNA (Nguyen LH et al. 2001). The enzyme is located in the cytoplasm and in the nuclear lumen. It shows antiviral activity against RNA viruses, including hepatitis C virus (HCV), hepatitis A virus (HAV) and yellow fever virus (YFV) (Pu Zhou Z et al. 2011). Inhibition of several viruses such as chikungunya virus (CHIKV) does not involve degradation of viral RNAs, but inhibition of translation of viral proteins . The ISG20 protein exerts translational control over a large group of non-endogenous RNA substrates, while endogenous transcripts are spared. This activity correlates with the protein's ability to localize to cytoplasmic processing bodies (Wu N et al. 2019).

It can also act as a master regulator of over a hundred interferon-stimulated genes, leading to inhibition of viral genome translation. It can probably play additional roles in the maturation of snRNAs and rRNAs as well as in ribosome biogenesis.

Diseases associated with ISG20 include hepatitis C and estrogen receptor-positive breast cancer.

UV and lupus erythematosus: To date, 14 UVB response genes (UVBACGs) correlating with lupus activity have been identified, including eight type I interferon-stimulated genes(IRF7, ISG20, ISG15, IFI44, IFITM1, MX1, LY6E, OASL) and 6 others (JUN, PTTG1, HLA-F, CAV1, HOPX, RPL3). Their significance has not yet been finally clarified.

1. Nguyen LH et al. (2001) The human interferon- and estrogen-regulated ISG20/HEM45 gene product degrades single-stranded RNA and DNA in vitro. Biochemistry 40:7174-7179.
2. Zhou Z et al. (2011) Antiviral activities of ISG20 in positive-strand RNA virus infections. Virology 409:175-188.
3. Wu N et al. (2019) The interferon stimulated gene 20 protein (ISG20) is an innate defense antiviral factor that discriminates self- versus non-self translation. PLoS Pathog 15:e1008093.