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 microm...真核细胞RNA的腺苷到肌苷（A-to-I）编辑，对于抵御自身免疫性疾病至关重要。该编辑过程由ADAR1介导，其中靶向先天免疫应答的细胞质同工型带有一个功能未知的Z-DNA结合结构域（Zα）。Zα还可结合RNA中的CpG重复序列，而此类重复序列正是Z-RNA形成的标志性特征。出乎意料的是，研究人员此前曾预测，且部分实验已证实，Zα可结合信使RNA（mRNA）与核糖体RNA（rRNA）内不含此类重复序列的特定区域。本研究借助核磁共振（NMR）、圆二色谱（circular dichroism）及其他生物物理手段，验证并表征了Zα与mRNA及rRNA片段的结合行为。研究结果显示，诸多RNA序列均可与Zα结合并采取Z-RNA构象。结合过程会伴随相邻A型区域的去稳定化，这一特征与B-Z DNA交界区域的相关观测结果高度相似。Zα与非CpG序列的结合具有特异性、协同性，且亲和力处于低微摩尔量级（原文未完整给出后续内容）。