ABSTRACT
This chapter describes a series of lucky events as I restarted my work on Z-DNA. I was able to synthesize a lot of published data into a new framework that led to the identification of a Z-box in a class of repeat elements able to form Z-RNAs. I was also able to provide the first genetic evidence that the ADAR1 Zα domain played an important role in regulating interferon responses. Variants in the Zα domain that were critical to the interaction with Z-DNA were causal factors of Aicardi-Goutières syndrome type 6, bilateral striatal necrosis/dystonia , and dyschromatosis symmetrica hereditaria. I also describe how Z-RNA is used as a mark of self by regulating filament formation by the dsRNA sensor MDA5. The importance of the events involving ADAR1 and its Zα domain in the silencing of immune responses by cancer cells also came to the fore at this time. The story is remarkable as it gives function to what previously was called junk DNA. The focus is on the Z-RNA-binding protein ADAR1 that performs the RNA editing function that was apparent from our first discoveries.
