Poster abstracts
Poster number 10 submitted by Marina Barriocanal
Several IFN-induced long noncoding RNAs regulate the antiviral response
Marina Barriocanal (Department of Gene Therapy and Regulation of Gene Expression, CIMA, University of Navarra), Victor Segura (Department of Bioinformatics, CIMA), Saba Valadkhan (Department of Molecular Biology and Microbiology, CWRU), Puri Fortes (Department of Gene Therapy and Regulation of Gene Expression, CIMA, University of Navarra)
Abstract:
Long noncoding RNAs (lncRNAs) have been described to have important roles in several processes such as cell differentiation and proliferation among others. However, the antiviral role of lncRNAs has remained largely unknown. We have identified several Interferon (IFN) Stimulated long noncoding RNAs (lncRNAs), that we call ISRs, by transcriptome analysis of cells treated or not with IFN.
Interestingly, some of these ISRs are located in the genome close to IFN stimulated genes (ISGs). lncBST2/BISPR, ISR12 and ISR8 are located close to BST2/tetherin, IL6 and IRF1 respectively. Downregulation of BISPR causes a decrease in the levels of BST2, indicating that BISPR is a positive regulator of BST2 expression. ISR12 seems to be a negative regulator of the expression of the distant ISG GBP1. Depletion of ISR12 does not affect its neighboring gene IL6. Instead, it leads to increased levels of the IFN induced gene GBP1 and, therefore, to decreased replication of Hepatitis C virus (HCV) in hepatocellular cell lines. Finally, clones with altered ISR8 expression obtained using the CRISPR-Cas system do not establish a successful IFN response. They fail to induce expression of several ISGs regulated by IRF1. This suggests that ISR8 works as a positive regulator of the IFN pathway.
In summary, our results show that lncRNAs induced after IFN treatment may function as positive or negative regulators of the IFN response. Molecular mechanism of the ISR-mediatd regulation of IFN response is currently under investigation.
Keywords: lncRNAs, IFN