We investigate interesting E3 mechanisms at the frontline between virus and cell, with some virology thrown in for good measure. Ub-er fun!
At the MRC-University of Glasgow Centre for Virus Research.
https://thefletcherlab.co.uk
Fletcher Lab
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Emma began her PhD in Sam Wilson's group at the CVR, where she and Sam developed an elegant approach for screening dsRNA in virus-infected cells in high throughput. Emma then used the famous Wilson Lab ISG screens to start screening for factors that inhibit human seasonal coronavirus, HCoV-OC43.
So, we think OAS2 exposes a hidden versatility of innate immunity: one gene ≠ one function... ≠ one PhD project!
Emma then moved to our group after the Wilson Lab relocated to Cambridge, and we began an iterative process of whittling down the screen to tractable targets for investigation.
Of two near-identical ~70 kDa isoforms that differ only by 4-/36-length c-terminal tails, only one restricts HCoV-OC43, while the other restricts cardiovirus A/Encephalomyocarditis virus. The shorter, anti-OC43 isoform restricts independently of 2-5A synthesis and RNase L.
OAS2 seemed an unlikely hit because HCoV-OC43, unlike some more distantly related betaCoVs e.g. SARS-CoV-2, encodes a phosphodiesterase (PDE). betaCoV PDEs are known to inhibit the OAS-RNase L pathway, an ancient antiviral partnership that relies on synthesis and detection of 2'-5'-oligoadenylates.
Delighted to share our article on the functional expansion of OAS2 via alt. splicing.
link.springer.com/article/10.1...
A tour de force from PhD student Emma Davies and friends.
Those little c-terminal tails, which sit at the opposite end of the OAS2 molecule from the site of (essential) co-translational lipidation, seem to hold the secret of split function.
