Abstract:

Flipons are genetically encoded elements that adopt different conformations, such as Z-DNA, G4-Quartets and Triplexes under physiological conditions. The structures are formed from simple sequence repeats and are recognized by structure-specific proteins that determine outcomes. I will discuss the biological function of Z-flipons, using the Z-RNA binding domain, Zα, of the RNA editing enzyme ADAR1 as an example. Variants of this domain are causal for the Type I Interferonopathy Aicardi Goutières syndrome. The mechanism by which Z-RNA formation prevents amplification by interferon response against self, double-stranded RNAs will be discussed. The concept of using flipons to encode binary switches, memory elements and other control elements of the genomic circuitry will be discussed.

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