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Title: RNA landscape of ILF3
Author: Watson, Samir Faysal
ISNI:       0000 0004 8510 4836
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2020
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During viral infections, the presence of viral-derived dsRNA triggers a translational shut-off response affecting translation of both host and viral-derived mRNAs. This response is mediated by the phosphorylation of Eukaryotic initiation factor 2α (eIF2α) by the double stranded RNA binding kinase PKR. However, the underlying mechanisms of this process are still not fully understood. Intriguingly, host antiviral genes escape this translational shut-off, suggesting a regulatory control mechanism that selectively allows the expression of essential self-defence genes. We have identified Interleukin enhancer binding factor 3 (ILF3) as an essential host factor required for efficient translation of the antiviral IFNB1 mRNA and a large subset of interferon-stimulated genes (ISGs) which are critical for establishing an effective antiviral state in the cell. By combining polysome profiling and high-throughput sequencing, we furthermore show that ILF3 is also required to trigger robust changes in transcription, alternative splicing and translation that arise from the activating the antiviral response. Our data suggests that ILF3-mediated regulation of RNA metabolism is necessary to establish a strong and vigorous cellular antiviral response.
Supervisor: Macias Ribela, Sara ; Cook, Atlanta Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: ILF3 ; translation ; virus ; infection ; innate immunity ; polysome profiling ; RNA ; sequencing ; interferon ; ISG ; interferon stimulated gene ; cytokine ; NF90 ; NF110