A25 - Structural mechanism of OAS1 activation by RNA modifications across species
The interferon-induced innate immune receptor OAS1 synthesizes 2´–5´oligoadenylates (2´–5´OA) upon sensing dsRNA in the cytosol. 2'–5'OA in turn binds and activates downstream latent RNase L, which degrades both viral and endogenous ssRNA, resulting in cell death. OAS1 is known to recognize short dsRNA (>18 bp) with a preference for a consensus sequence that allows OAS1 to contact dsRNA at two segments of the minor groove of the dsRNA helix. Besides being one of the first interferon-induced antiviral pathways to be discovered, little is known about the exact nature of the preferred dsRNA ligand for OAS1 activation. Recently, 5´ppp-RNA triggered tumor cell death was shown by members of this consortium to be dependent on the OAS1–RNase L activation. This project aims to uncover the structural and biochemical mechanism for the proper activation of OAS1 by dsRNA, which also explains the effects of modifications, especially 5'-triphosphate, and RNA length-dependent recognition by OAS1, taking into account its sequence specificity. In general, we want to define which known characteristics of dsRNA have the greatest impact on the activity of OAS1.
Dr. Carina de Oliveira MannSchool of Natural Sciences, TU Munich +49 (0)89 4140-7360 External web links: |
