The Unusual Role of Ribonuclease L in Innate Immunity

Ribonuclease L is an endonuclease that is activated as part of the dsRNA-driven innate immune response. Active RNase L cleaves pathogenic RNAs as a way to eliminate infections. However, there are additional and unexpected ways that RNase L causes changes in the host that promote an immune response and contribute to its role in host defense. Central to these unconventional mechanisms is the observation that RNase L also degrades the mRNA of the host. In turn, mRNA fragments that RNase L generates can be translated. This causes activation of a ribosome collision sensor that leads to downstream signaling and cell death. Additionally, the liberation of RNA binding proteins after RNA decay appears to affect gene expression. In this review, we discuss these and other recent advances that focus on novel and unusual ways RNase L contributes to innate immunity.