The innate immune system is the first line of defense against invading pathogens such as viruses. A fast and efficient innate immune response depends upon an early recognition of the pathogen by so-called pattern-recognition receptors (PRRs). One of the most important PRRs in terms of recognition of viral RNAs in the cytoplasm is the retinoic acid inducible gene I (RIG-I). Following viral infection, RIG-I predominantly recognizes short double-stranded RNAs (dsRNA) containing triphosphate at their 5’ end and triggers a distinct signal transduction pathway leading to induction of cytokines such as interferon (IFN) as well as other antiviral proteins. Activation of RIG-I is regulated at several levels by cellular proteins in order to both prevent undue activation of the innate immune response and to increase the efficiency of RIG-I-mediated signaling. For example, following recognition of viral RNA, RIG-I binds free unanchored K63-linked polyubiquitin chains and this interaction with polyubiquitin is required for its activation. However, our collaborator Saumendra N. Sarkar from the University of Pittsburgh Cancer Institute, USA, has recently discovered that another IFN-stimulated protein known as the oligoadenylate synthetase-like protein (OASL) can act as a substitute for polyubiquitin in activation of RIG-I. Through its two C-terminal ubiquitin-like repeats, OASL interacts with the RIG-I caspase recruitment domains (CARD) and thus mimics the role of polyubiquitin. However, how the remaining N-terminal part of OASL contributes to the activation of RIG-I is not clear although it was shown to interact with RIG-I as well. Here, we show that the N-terminal domain of OASL binds dsRNA and that this binding is required in order for OASL to promote RIG-I activation. This suggests that OASL acts not only as a cofactor for RIG-I activation but also as a PRR.