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Viral infections pose significant threats to human health, leading to a diverse spectrum of infectious diseases. The innate immune system serves as the primary barrier against viruses and bacteria in the early stages of infection. A rapid and forceful antiviral innate immune response is triggered by distinguishing between self-nucleic acids and viral nucleic acids. RNA-binding proteins (RBPs) are a diverse group of proteins which contain specific structural motifs or domains for binding RNA molecules. In the last decade, numerous of studies have outlined that RBPs influence viral replication via diverse mechanisms, directly recognizing viral nucleic acids and modulating the activity of pattern recognition receptors (PRRs). In this review, we summarize the functions of RBPs in regulation of host-virus interplay by controlling the activation of PRRs, such as RIG-I, MDA5, cGAS and TLR3. RBPs are instrumental in facilitating the identification of viral RNA or DNA, as well as viral structural proteins within the cellular cytoplasm and nucleus, functioning as co-receptor elements. On the other hand, RBPs are capable of orchestrating the activation of PRRs and facilitating the transmission of antiviral signals to downstream adaptor proteins by post-translational modifications or aggregation. Gaining a deeper comprehension of the interaction between the host and viruses is crucial for the development of novel therapeutics targeting viral infections. [ABSTRACT FROM AUTHOR]

Innate immunity is the first line of defense against infections, which functions as a significant role in resisting pathogen invasion. Rapid immune response is initiated by pattern recognition receptors (PRRs) quickly distinguishing "self" and "non‐self." Upon evolutionarily conserved pathogen‐associated molecular pattern (PAMP) is recognized by PRRs, innate immune response against infection is triggered via an orchestration of molecular interaction, cytokines cascades, and immune cells. RIG‐I plays a critical role in type I interferon (IFN‐I) production by direct recognition of cytoplasmic double‐stranded viral RNA. However, the activation mechanism of RIG‐I is incompletely understood. In this study, we reported RNA‐binding protein ZFP36 as a positive regulator of RIG‐I‐mediated IFN‐I production. ZFP36 is a member of Zinc finger proteins (ZFPs) characterized by the zinc finger (ZnF) motif, which broadly involved gene transcription and signal transduction. However, its role in regulating antiviral innate immune signaling is still unclear. We found that ZFP36 associates with RIG‐I and potentiates the FN‐β production induced by SeV. Mechanistically, ZFP36 promotes K63‐linked polyubiquitination of RIG‐I, mostly at K154/K164/K172, thereby facilitating the activation of RIG‐I during infection. While the mutant ZFP36 (C118S/C162S) failed to increase polyubiquitination of RIG‐I and SeV induced FN‐β. Our findings collectively demonstrated that ZFP36 acts as a positive regulator in antiviral innate immunity by targeting RIG‐I for K63‐linked ubiquitination, thus improving our understanding of the activation mechanism of RIG‐I. [ABSTRACT FROM AUTHOR]