Long non-coding RNAs (lncRNAs) can play a major role in modulating innate immune responses by acting as positive or negative regulators. LncRNAs can mediate protein interactions with chromatin and other proteins by serving as scaffolds, decoys, and guides. The expression pattern of most lncRNAs is cell and context specific, making them attractive targets for precise therapeutic intervention. However, only a small number of lncRNAs have been well characterized due to their low abundance, context dependent expression, and complex modes of action. We have previously identified lncRNA VILMIR as an interferon-stimulated gene that regulates host interferon response to viral infection and interferon treatment. In this study, we investigated molecular mechanisms through which VILMIR modulates host immune response.
Using in vitro RNA pulldown assays followed by in vivo RNA immunoprecipitation validation, we identified several VILMIR-interacting proteins, including FUBP1, an RNA-binding protein implicated in transcriptional regulation. Mapping experiments with truncated VILMIR fragments revealed specific regions involved in protein binding.
Our findings suggest that VILMIR modulates transcription of interferon-stimulated genes by forming an RNA-protein complex with FUBP1.
Future studies will focus on elucidating how the VILMIR-FUBP1 complex influences the transcriptional landscape during viral infection and exploring its potential as a therapeutic target to fine-tune antiviral immune responses.
National Institutes of Health Grant R21AI147187
Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)
Nasif Mahmood, Kristen John, Alexandra Istishin et al.· Journal of Immunology· 0 citations
Two novel interferon-responsive human lncRNAs that may play important roles in the regulation of the host interferon response across different cell types are identified.
Alexandra Istishin, Kristen John, Ethan Smith et al.· Journal of Immunology· 0 citations
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