Data for publication: Recognition of non-CpG repeats in Alu and ribosomal RNAs by the Z-RNA binding domain of ADAR1 induces A-Z junctions

Adenosine-to-inosine (A-to-I) editing of eukaryotic cellular RNAs is
essential for protection against auto-immune disorders. Editing is carried
out by ADAR1, whose innate immune response-specific cytoplasmic isoform
possesses a Z-DNA binding domain (Zα) of unknown function. Zα also binds
to CpG repeats in RNA, which are a hallmark of Z-RNA formation.
Unexpectedly, Zα has been predicted — and in some cases even shown — to
bind to specific regions within mRNA and rRNA devoid of such repeats.
Here, we use NMR, circular dichroism, and other biophysical approaches to
demonstrate and characterize the binding of Zα to mRNA and rRNA fragments.
Our results reveal a broad range of RNA sequences that bind to Zα and
adopt Z-RNA conformations. Binding is accompanied by destabilization of
neighboring A-form regions which is similar in character to what has been
observed for B-Z-DNA junctions. The binding of Zα to non-CpG sequences is
specific, cooperative and occurs with an affinity in the low micromolar
range. This work allows us to propose a model for how Zα could influence
the RNA binding specificity of ADAR1.