Z-RNA is a higher-energy, left-handed conformation of RNA, whose function has remained elusive. A growing body of work alludes to regulatory roles for Z-RNA in the immune response. Here, we review how Z-RNA features present in cellular RNAs-especially containing retroelements-could be recognized by a family of winged helix proteins, with an impact on host defense. We also discuss how mutations to specific Z-contacting amino acids disrupt their ability to stabilize Z-RNA, resulting in functional losses. We end by highlighting knowledge gaps in the field, which, if addressed, would significantly advance this active area of research.
Keywords: E3L; Z-D/RNA-binding protein 1 (ZBP1); Z-RNA; Zα; adenosine deaminase acting on RNA (ADAR1); innate immune response; retroelement.
© 2023 Nichols et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.