Double-stranded RNAs containing multiple IU pairs are sufficient to suppress interferon induction and apoptosis
| Autor: | Patrice Vitali, A. D. J. Scadden |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Regulation of gene expression
0303 health sciences viruses 030302 biochemistry & molecular biology virus diseases RNA Biology Molecular biology 03 medical and health sciences Structural Biology Apoptosis Interferon medicine IRF3 Inosine Molecular Biology Gene 030304 developmental biology Interferon regulatory factors medicine.drug |
| Zdroj: | Nature Structural & Molecular Biology. 17:1043-1050 |
| ISSN: | 1545-9985 1545-9993 |
| DOI: | 10.1038/nsmb.1864 |
| Popis: | Adenosine deaminases acting on RNA (ADARs) catalyze hyperediting of long double-stranded RNAs (dsRNAs), whereby up to 50% of adenosines are converted to inosine (I). Although hyperedited dsRNAs (IU-dsRNAs) have been implicated in various cellular functions, we now provide evidence for another role. We show that IU-dsRNA suppresses the induction of interferon-stimulated genes (ISGs) and apoptosis by poly(IC). Moreover, we show that IU-dsRNA inhibits the activation of interferon regulatory factor 3 (IRF3), which is essential for the induction of ISGs and apoptosis. Finally, we speculate that the inhibition of IRF3 results from specific binding of IU-dsRNA to MDA-5 or RIG-I, both of which are cytosolic sensors for poly(IC). Although our data are consistent with a previous study in which ADAR1 deletion resulted in increased expression of ISGs and apoptosis, we show that IU-dsRNA per se suppresses ISGs and apoptosis. We therefore propose that any IU-dsRNA generated by ADAR1 can inhibit both pathways. |
| Databáze: | OpenAIRE |
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