Orchestration of the activation of protein kinase R by the RNA-binding motif

Abstract

The protein kinase R (PKR) constitutes part of the host antiviral response. PKR activation is regulated by the N-terminus of protein, which encodes tandem RNA-binding motifs (RBMs). The full capabilities of RBMs from PKR and other proteins have surpassed the narrow specificities initially determined as merely binding double-stranded RNA. Recognition of the increased affinity of the RBM for additional RNA species has established an immunological distinction by which PKR can detect exogenous RNAs, as well as identified PKR-mediated expression of specific endogenous genes. Furthermore, as RBMs also mediate interactions with other proteins, including PKR itself, this motif connects PKR to the broader RNA metabolism. Given the fundamental importance of protein-RNA interactions, not only in the innate immune response to intracellular pathogens, but also to coordinate the cellular replication machinery, there is considerable interest in the mechanisms by which proteins recognize and respond to RNA. This review appraises our understanding of how PKR activity is modulated by the RBMs.