RNase L limits host and viral protein synthesis via inhibition of mRNA export

RNase L is widely thought to limit viral protein synthesis by cleaving host rRNA and viral mRNA, resulting in translation arrest and viral mRNA degradation. Here, we show that the mRNAs of dengue virus and influenza A virus largely escape RNase L-mediated mRNA decay, and this permits viral protein production. However, activation of RNase L arrests nuclear mRNA export, which strongly inhibits influenza A virus protein synthesis and reduces cytokine production. The heterogeneous and temporal nature of the mRNA export block in individual cells permits sufficient production of antiviral cytokines from transcriptionally induced host mRNAs. This defines RNase L-mediated arrest of mRNA export as a key antiviral shutoff and cytokine regulatory pathway.

Automated summary

The study demonstrates that RNase L-mediated mRNA decay does not completely limit protein synthesis of dengue virus and influenza A virus, as their mRNAs largely escape this process. However, activation of RNase L inhibits nuclear mRNA export, thereby restricting influenza A virus protein synthesis and cytokine production.