A Z-DNA BINDING DOMAIN PRESENT IN THE HUMAN EDITING ENZYME, DOUBLE-STRANDED-RNA ADENOSINE-DEAMINASE

Editing of RNA changes the read-out of information from DNA by alterin g the nucleotide sequence of a transcript, One type of RNA editing fou nd in all metazoans uses double-stranded RNA (dsRNA) as a substrate an d results in the deamination of adenosine to give inosine, which is tr anslated as guanosine, Editing thus allows variant proteins to be prod uced from a single pre-mRNA, A mechanism by which dsRNA substrates for m is through pairing of intronic and exonic sequences before the remov al of noncoding sequences by splicing, Here we report that the RNA edi ting enzyme, human dsRNA adenosine deaminase (DRADA1, or ADAR1) contai ns a domain (Z alpha) that binds specifically to the left-handed Z-DNA conformation with high affinity (K-D = 4 nM), As formation of Z-DNA i n vivo occurs 5' to, or behind, a moving RNA polymerase during transcr iption, recognition of Z-DNA by DRADA1 provides a plausible mechanism by which DRADA1 can be targeted to a nascent RNA so that editing occur s before splicing, Analysis of sequences related to Z alpha has allowe d identification of motifs common to this class of nucleic acid bindin g domain.