The canonical antiviral protein oligoadenylate synthetase 1 elicits antibacterial functions by enhancing IRF1 translation.
Munesh K HarioudhJoseph PerezLomon SoMayank MaheshwariThomas S EbertVeit HornungRam SavanA Rouf BandayMichael S DiamondVijay A RathinamSaumendra N SarkarPublished in: Immunity (2024)
An important property of the host innate immune response during microbial infection is its ability to control the expression of antimicrobial effector proteins, but how this occurs post-transcriptionally is not well defined. Here, we describe a critical antibacterial role for the classic antiviral gene 2'-5'-oligoadenylate synthetase 1 (OAS1). Human OAS1 and its mouse ortholog, Oas1b, are induced by interferon-γ and protect against cytosolic bacterial pathogens such as Francisella novicida and Listeria monocytogenes in vitro and in vivo. Proteomic and transcriptomic analysis showed reduced IRF1 protein expression in OAS1-deficient cells. Mechanistically, OAS1 binds and localizes IRF1 mRNA to the rough endoplasmic reticulum (ER)-Golgi endomembranes, licensing effective translation of IRF1 mRNA without affecting its transcription or decay. OAS1-dependent translation of IRF1 leads to the enhanced expression of antibacterial effectors, such as GBPs, which restrict intracellular bacteria. These findings uncover a noncanonical function of OAS1 in antibacterial innate immunity.
Keyphrases
- dendritic cells
- immune response
- endoplasmic reticulum
- binding protein
- silver nanoparticles
- poor prognosis
- listeria monocytogenes
- endothelial cells
- regulatory t cells
- staphylococcus aureus
- small molecule
- gene expression
- wound healing
- microbial community
- reactive oxygen species
- dna methylation
- cell proliferation
- cell death
- transcription factor
- toll like receptor
- inflammatory response
- type iii
- amino acid