Role of helical structure and dynamics in oligoadenylate synthetase 1 (OAS1) mismatch tolerance and activation by short dsRNAs

Abstract

Significance The innate immune system is a collection of essential frontline defenses against infectious pathogens such as viruses. Currently, however, we do not fully understand how one innate immune sensor of double-stranded RNA (dsRNA), oligoadenylate synthetase 1 (OAS1), is regulated in the absence of infection, nor the specific features of dsRNA molecules that lead to potent OAS1 activation. Here, we uncover a molecular basis for how sequence-independent features of short dsRNAs influence the extent of OAS1 activation. We also find that OAS1 is able to sense inosine-containing dsRNAs, suggesting that RNA editing may not be a protective mechanism to avoid aberrant cellular activation of OAS1 as has been proposed for other dsRNA sensing innate immune proteins.