RNASE L

RNASEL encodes RNase L, an interferon-inducible endoribonuclease that functions as a central effector of the 2′-5′-oligoadenylate synthetase (OAS)-RNase L pathway, a conserved arm of innate antiviral immunity[1][2]. Upon recognition of viral double-stranded RNA, OAS enzymes synthesize 2′-5′-linked oligoadenylates (2-5A), which bind and activate RNase L, leading to the cleavage of cellular and viral RNA and suppression of viral replication[1][3][4]. Mechanistically, RNase L-mediated RNA fragmentation not only restricts pathogen replication but also promotes downstream stress and immune signaling, including activation of ZAKα-dependent ribotoxic stress pathways and antiviral transcriptional programs[2]. Beyond classical antiviral defense, the OAS-RNase L axis regulates inflammatory responses, and genetic defects in this pathway have been linked to severe inflammatory manifestations associated with SARS-CoV-2 infection, highlighting its importance in immune homeostasis[5]. Disease-relevant studies further demonstrate that RNase L participates in tissue-specific biological processes, including the regulation of wound-induced hair follicle neogenesis and epithelial regeneration through modulation of innate immune signaling pathways[6]. Compared with related OAS family members that function primarily as upstream sensors and 2-5A synthetases, RNase L serves as the terminal catalytic effector that directly executes RNA degradation after pathway activation[1][3]. For experimental applications, pharmacological inhibition of RNase L has been achieved using small-molecule inhibitors that block RNase L activity and prevent excessive RNA cleavage, providing useful tools for mechanistic studies of innate immunity, inflammation, and RNA biology[7].