Human RNase 2 is essential for macrophage response to viral RNA

SUMMARY RNase 2 is the most abundant human RNase A member in macrophages and its expression is activated upon exposure to viruses. Here, we explored the protein role by co-transcriptomics analysis of wild-type (WT) and RNase 2-knock-out (KO) macrophages in absence/presence of a virus-derived single-stranded RNA (ssRNA40). Results revealed that RNase 2 is key for maintaining cell homeostasis. Lacking RNase 2 induced the expression of stress-response markers under basal conditions and abolished the antiviral response of cells exposed to ssRNA40. In contrast, the up-regulated genes in WT macrophages participate in pro-inflammatory signaling response through TLR8-dependent pathways and antiviral immunity, with activation of MAPK and JAK-STAT pathways. Complementarily, we identified five top tRNA-derived small RNAs (tDRs) in response to ssRNA40 related to RNase 2, showing a preferential cleavage sites at CA and uridine rich regions of anticodon loops. Results highlight the essential roles of RNase 2 in antiviral response and inflammatory processes. Competing Interest Statement The authors have declared no competing interest.