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

• DOI: 10.1038/s41467-021-21039-0
• Publication Date: 2021-02-04T11:08:10Z
• Authors: Parker J. Nichols; Shaun Bevers; Morkos Henen; Jeffrey S. Kieft; Quentin Vicens; Beat Vögeli
• Keywords: 0301 basic medicine; Adenosine Deaminase; Science; Circular Dichroism; Q; RNA-Binding Proteins; Article; Immunity, Innate; Recombinant Proteins; 3. Good health; 03 medical and health sciences; Protein Domains; Alu Elements; RNA, Ribosomal; Nucleic Acid Conformation; Nuclear Magnetic Resonance, Biomolecular; RNA Recognition Motif

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