A Left-Handed RNA Double Helix Bound by the Zα Domain of the RNA-Editing Enzyme ADAR1

SummaryThe A form RNA double helix can be transformed to a left-handed helix, called Z-RNA. Currently, little is known about the detailed structural features of Z-RNA or its involvement in cellular processes. The discovery that certain interferon-response proteins have domains that can stabilize Z-RNA as well as Z-DNA opens the way for the study of Z-RNA. Here, we present the 2.25 Å crystal structure of the Zα domain of the RNA-editing enzyme ADAR1 (double-stranded RNA adenosine deaminase) complexed to a dUr(CG)3 duplex RNA. The Z-RNA helix is associated with a unique solvent pattern that distinguishes it from the otherwise similar conformation of Z-DNA. Based on the structure, we propose a model suggesting how differences in solvation lead to two types of Z-RNA structures. The interaction of Zα with Z-RNA demonstrates how the interferon-induced isoform of ADAR1 could be targeted toward selected dsRNAs containing purine-pyrimidine repeats, possibly of viral origin