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bioRxiv · 10.64898/2025.12.03.691791

Human RNase 2 is essential for macrophage response to viral RNA

Li, J.·Lu, L.·Anguita, R.·Julian, E.·Boix, E.
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Abstract

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.

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Li, J., Lu, L., Anguita, R., Julian, E., Boix, E.. 2025-12-03. Human RNase 2 is essential for macrophage response to viral RNA. https://doi.org/10.64898/2025.12.03.691791

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