Oligoadenylate synthase-like (OASL) proteins: dual functions and associations with diseases

Abstract

The study of antiviral pathways to reveal methods for the effective response and clearance of virus is closely related to understanding interferon (IFN) signaling and its downstream target genes, IFN-stimulated genes. One of the key antiviral factors induced by IFNs, 2'-5' oligoadenylate synthase (OAS), is a well-known molecule that regulates the early phase of viral infection by degrading viral RNA in combination with RNase L, resulting in the inhibition of viral replication. In this review, we describe OAS family proteins from a different point of view from that of previous reviews. We discuss not only RNase L-dependent (canonical) and -independent (noncanonical) pathways but also the possibility of the OAS family members as biomarkers for various diseases and clues to non-immunological functions based on recent studies. In particular, we focus on OASL, a member of the OAS family that is relatively less well understood than the other members. We will explain its anti- and pro-viral dual roles as well as the diseases related to single-nucleotide polymorphisms in the corresponding gene.

Figure 1

The OAS family in antiviral pathways. Following virus infection of a host cell, viral dsRNA stimulates OAS1, OAS2 and OAS3 and leads to the synthesis of 2′-5′ oligoA and RNase L activation. Activated RNase L cleaves viral and cellular RNA. MDA5 and RIG-I detect cleaved viral RNA, thereby promoting the activation of IRF3 and IRF7. The hOASL binds to RIG-I and enhances the sensitivity of RIG-I signaling through the UBL domain, whereas the mOASL1 binds to IRF7 mRNA and inhibits the translation of IRF7.