RLR-mediated IFN signaling and aberrant activation

Abstract

Interferon (IFN) signaling is important for host cells in defending microorganisms. “Self” and “non-self” recognition is the key step for proper IFN functioning. Pathogen-derived double-stranded RNAs (dsRNAs) are immunogenic to the cytosolic sensor, RIG-I and MDA5. Together known as RIG-I-like receptors (RLRs), they form filament along the length of dsRNA substrate which in turn activate downstream cascades. Despite RLRs themselves and host encoded regulators managing to avoid self-intolerance, extensive studies in recent years uncovered that the boundary of “self” and “non-self” can be vague. Retrotransposon elements embedded in the genome of humans can turn into RLR ligands under certain circumstances, like incorrect RNA metabolism or epigenetic drug treatment, which in turn, lead to IFN signaling activation. The consequences of such activation can be different according to different circumstances. Here, we summarized the biological features of RLR-mediated IFN signaling and discussed aberrant IFN signaling through RLRs, including situations of gene mutations, irradiation, and anti-cancer drug treatment. We speculated that combining current cancer therapy and RLR-mediated IFN signaling activation would bring beneficial effects to cancer treatment.