Innate RNA sensor (PRR)

Innate RNA sensors are a specialized class of pattern recognition receptors (PRRs) that detect the presence of non-self or mislocalized RNA molecules within the cell (Chow et al., 2018, Annual Review of Immunology). These sensors are strategically localized in different cellular compartments, including the endosomes (e.g., TLR3, TLR7, and TLR8) and the cytoplasm (e.g., RIG-I, MDA5, and PKR), to monitor for viral or damaged host RNA (Rehwinkel and Gack, 2020, Nature Reviews Immunology). Upon binding to specific RNA ligands, such as double-stranded RNA or 5-prime-triphosphate RNA, these receptors initiate signaling pathways that culminate in the production of type I interferons and pro-inflammatory cytokines (Wu and Chen, 2014, Annual Review of Immunology). This response is critical for establishing an antiviral state and orchestrating the adaptive immune response (Schlee and Hartmann, 2016, Nature Reviews Immunology). Dysregulation of these sensors is linked to various pathologies, including autoimmune diseases like systemic lupus erythematosus and Aicardi-Goutières syndrome, where the sensors mistakenly respond to endogenous RNA (Crow and Stetson, 2022, Journal of Clinical Investigation). In oncology, agonists of innate RNA sensors are being investigated as potent immunotherapeutic agents to turn cold tumors hot by stimulating the tumor microenvironment (Zhu et al., 2019, Journal of Hematology & Oncology). Conversely, small molecule inhibitors are under development to mitigate the chronic inflammation associated with overactive RNA sensing pathways (Vasilikos et al., 2023, Frontiers in Immunology).

Other names

RNA pattern recognition receptorCytosolic RNA sensorEndosomal RNA sensorRNA-sensing receptorRIG-I-like receptorToll-like receptor (RNA-specific)Nucleic acid sensor

Agonism of these sensors triggers the production of type I interferons and pro-inflammatory cytokines to enhance antiviral or antitumor immunity, while antagonism is aimed at reducing pathological inflammation in autoimmune disorders.