Work

RNA‐Binding Protein RBM25 Targets the mRNA Stability of GTPase Rab22a to Restrict Viral Entry and Infection

Year: 2026

Type: article

Abstract: Viral infections trigger complex host defense responses, yet many key regulatory mechanisms remain undefined. Here, we identify the RNA-binding protein RBM25 as a potent, broad-spectrum host antiviral factor, independently of the type I interferon (IFN-I) pathway. Viral infection downregulates RBM25 expression, and RBM25-deficient mice exhibit enhanced susceptibility to multiple viruses and more aggravated tissue damage. In vitro, RBM25 inhibits the viral infection and replication across a spectrum of RNA and DNA viruses. Mechanistically, the antiviral activity of RBM25 is independent of IFN-I signaling and is instead linked to an early blockade in the viral life cycle. RBM25 specifically impedes viral cell entry through the suppression of the host GTPase Rab22a, a well-known facilitator of viral endocytosis. Virus infection-elicited downregulation of RBM25 results in Rab22a upregulation, which consequently potentiates viral entry. Furthermore, we elucidate the post-transcriptional mechanisms that RBM25 interacts with RC3H1 (ring finger and CCCH-type domains 1) to form an RNA-binding complex that binds and destabilizes Rab22a mRNA, thereby limiting its protein translation. Collectively, our work unveils the RBM25/RC3H1-Rab22a axis as an interferon-independent post-transcriptional pathway that governs viral entry by modulating the mRNA stability of a critical host endocytosis factor, which presents a potential target for developing broad-spectrum antiviral strategies.

Source: Advanced Science

DOI: 10.1002/advs.76160