The RNA-editing enzyme ADAR1 is localized to the nascent ribonucleoproteinmatrix on Xenopus lampbrush chromosomes but specifically associates with an atypical loop

Double-stranded RNA adenosine deaminase (ADAR1, dsRAD, DRADA) converts aden osines to inosines in double-stranded RNAs. Few candidate substrates for AD AR1 editing are known at this point and it is not known how substrate recog nition is achieved. In some cases editing sites are defined by basepaired r egions formed between intronic and exonic sequences, suggesting that the en zyme might function cotranscriptionally. We have isolated two variants of X enopus laevis ADAR1 for which no editing substrates are currently known. We demonstrate that both Variants of the enzyme are associated with transcrip tionally active chromosome loops suggesting that the enzyme acts cotranscri ptionally. The widespread distribution of the protein along the entire chro mosome indicates that ADAR1 associates with the RNP matrix in a substrate-i ndependent manner. Inhibition of splicing, another cotranscriptional proces s, does not affect the chromosomal localization of ADAR1, Furthermore, we c an show that the enzyme is dramatically enriched on a special RNA-containin g loop that seems transcriptionally silent. Detailed analysis of this loop suggests that it might represent a site of ADAR1 storage or a site where ac tive RNA editing is taking place. Finally, mutational analysis of ADAR1 dem onstrates that a putative Z-DNA binding domain present in ADAR1 is not requ ired for chromosomal targeting of the protein.