TRIM25 and DEAD-Box RNA Helicase DDX3X Cooperate to Regulate RIG-I-Mediated Antiviral Immunity
| Autor: | Steven M. Heaton, Oded Kleifeld, Michelle D Audsley, Natalie A. Borg, Sarah C. Atkinson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
viruses
NS1 DEAD-box RNA Helicases Tripartite Motif Proteins Ubiquitin Interferon Receptors Immunologic Biology (General) Promoter Regions Genetic Spectroscopy E3 ligase 0303 health sciences RIG-I 030302 biochemistry & molecular biology General Medicine RNA Helicase A 3. Good health Computer Science Applications Cell biology Ubiquitin ligase antiviral immunity RLR signalling Chemistry Influenza A virus DEAD Box Protein 58 DDX3X influenza Protein Binding Signal Transduction medicine.drug TRIM25 DEAD-box helicase DEAD box QH301-705.5 Ubiquitin-Protein Ligases Biology ubiquitination IFN Antiviral Agents Article Catalysis Cell Line Inorganic Chemistry 03 medical and health sciences medicine Humans Physical and Theoretical Chemistry QD1-999 Molecular Biology 030304 developmental biology Organic Chemistry Immunity RNA virus biology.organism_classification HEK293 Cells Gene Expression Regulation biology.protein Interferons Transcription Factors |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 16 International Journal of Molecular Sciences, Vol 22, Iss 9094, p 9094 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22169094 |
| Popis: | The cytoplasmic retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) initiate interferon (IFN) production and antiviral gene expression in response to RNA virus infection. Consequently, RLR signalling is tightly regulated by both host and viral factors. Tripartite motif protein 25 (TRIM25) is an E3 ligase that ubiquitinates multiple substrates within the RLR signalling cascade, playing both ubiquitination-dependent and -independent roles in RIG-I-mediated IFN induction. However, additional regulatory roles are emerging. Here, we show a novel interaction between TRIM25 and another protein in the RLR pathway that is essential for type I IFN induction, DEAD-box helicase 3X (DDX3X). In vitro assays and knockdown studies reveal that TRIM25 ubiquitinates DDX3X at lysine 55 (K55) and that TRIM25 and DDX3X cooperatively enhance IFNB1 induction following RIG-I activation, but the latter is independent of TRIM25’s catalytic activity. Furthermore, we found that the influenza A virus non-structural protein 1 (NS1) disrupts the TRIM25:DDX3X interaction, abrogating both TRIM25-mediated ubiquitination of DDX3X and cooperative activation of the IFNB1 promoter. Thus, our results reveal a new interplay between two RLR-host proteins that cooperatively enhance IFN-β production. We also uncover a new and further mechanism by which influenza A virus NS1 suppresses host antiviral defence. |
| Databáze: | OpenAIRE |
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