A Z-RNA nanoswitch encoded by ‘junk DNA’ turns-off immune responses against self

In a paper published in the May 13th, 2021 issue of PLOS Genetics, a Z-RNA nanoswitch that regulates interferon immune responses is described. The switch, less than 5 nanometer in length, is based on sequences, called flipons, that change outcomes by altering their three dimensional conformation. The Z-RNA nanoswitch flips from the shorter right-handed A-RNA helix (“on”) to the longer left-handed Z-RNA helix (“off”). The flip ends immune responses against self RNAs, but not against viruses. Surprisingly, the Z-RNA nanoswitch sequence is encoded by “junk DNA.” The Z-RNA nanoswitch is used by some cancers to silence anti-tumor immune responses. In other cases, a malfunction of the Z-RNA nanoswitch causes inflammatory disease.

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