Dual mechanisms of ribonucleases in pathogen-host interactions

Abstract Ribonucleases (RNases) are fundamental regulators of RNA metabolism that function as both virulence determinants and host defense effectors. During infection, pathogens exploit RNase activities to ensure replication fidelity, reprogram host gene expression, and evade immune surveillance, whereas hosts deploy RNase arsenal to restrict pathogen proliferation and amplify antimicrobial signaling. Despite extensive characterization of individual enzymes, an integrated mechanistic framework spanning viral and bacterial systems remains elusive, and the therapeutic potential of targeting conserved RNA processing pathways is underexplored. Here, we systematically describe RNase-mediated mechanisms across representative pathogens, including severe acute respiratory syndrome coronavirus 2, influenza A virus, Staphylococcus aureus and Pseudomonas aeruginosa . Viral strategies that ensure genome integrity, degrade immunostimulatory RNAs, and silence host immune gene expression are outlined, along with bacterial systems wherein RNases coordinate virulence gene expression, metabolic adaptation, and the transition between acute and chronic infection states. Host countermeasures, ranging from membrane disruption and RNA decay pathways to ribotoxic stress responses, are further explored. By revealing the convergent evolutionary principles of RNA metabolism hijacking and the double-edged nature of shared enzymatic pathways, this review highlights the spatiotemporal precision of RNA processing as a potential therapeutic target for combating antimicrobial resistance and emerging viral variants.