Structure of human IFIT1 with capped RNA reveals adaptable mRNA binding and mechanisms for sensing N1 and N2 ribose 2′-O methylations (original) (raw)

IFIT1 is a key immune factor that inhibits viral mRNA translation by preferentially recognizing nonself capped mRNAs. The study presents crystal structures of RNA-bound IFIT1, demonstrating a flexible RNA-binding tunnel structure that allows for the discrimination of host versus viral mRNA based on specific methylation patterns at the N1 and N2 positions. Functionally, N1 and N2 ribose 2′-O methylations impact IFIT1 binding and translation inhibition, suggesting a mechanism for how IFIT1 mediates antiviral responses against modified viral RNAs.