Abstract
Left-handed Z-DNA/Z-RNA is bound with high affinity by the Zα domain protein family that includes ADAR (a double-stranded RNA editing enzyme), ZBP1 and viral orthologs regulating innate immunity. Loss-of-function mutations in ADAR p150 allow persistent activation of the interferon system by Alu dsRNAs and are causal for Aicardi-Goutières Syndrome. Heterodimers of ADAR and DICER1 regulate the switch from RNA- to protein-centric immunity. Loss of DICER1 function produces age-related macular degeneration, a different type of Alu-mediated disease. The overlap of Z-forming sites with those for the signal recognition particle likely limits invasion of primate genomes by Alu retrotransposons.
MeSH terms
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Adenosine Deaminase / genetics
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Adenosine Deaminase / metabolism
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Alu Elements / genetics
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Amino Acid Sequence
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Animals
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Autoimmune Diseases of the Nervous System / genetics*
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Binding Sites
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DEAD-box RNA Helicases / genetics
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DNA, Z-Form / chemistry
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DNA, Z-Form / genetics*
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DNA, Z-Form / metabolism*
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Humans
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Loss of Function Mutation
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Nervous System Malformations / genetics*
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Nucleic Acid Conformation
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Protein Binding
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RNA, Double-Stranded / metabolism
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism
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Ribonuclease III / genetics
Substances
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DNA, Z-Form
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RNA, Double-Stranded
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RNA-Binding Proteins
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DICER1 protein, human
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Ribonuclease III
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ADAR protein, human
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ADARB1 protein, human
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Adenosine Deaminase
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DEAD-box RNA Helicases
Supplementary concepts
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Aicardi-Goutieres syndrome