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ADAR1 p150-mediated double-stranded (dsRNA) adenosine-inosine RNA editing can prevent the activation of MDA5, leading to abnormal activation of innate immunity
Like DNA, RNA molecules contain information through a unique combination of four different nucleotides
There are two ADAR1 proteins in mouse cells: p110 and p150
The lead author of the study, Taisuke Nakahama, said: "The mutations in ADAR1 p150, including the domain that recognizes Z-RNA, are all related to an inherited inflammatory disease called Aicardi-Goutières syndrome (AGS)
To investigate this, the research team created genetically modified laboratory mice that have point mutations in both alleles of the gene encoding ADAR1 p150
"Mutant mice have abnormal development of organs, including key organs such as the brain, spleen, and colon," senior author Yukio Kawahara explains
The mutant mice also showed high levels of interferon-stimulating genes, leading to a chronic inflammatory state
Nakahama explained: "Our work shows that the interaction of this region with Z-RNA is a key initial step to prevent the immune system from thinking this molecule is a foreign invader
This study determined that improper Z-RNA recognition is a factor in the pathogenesis of AGS
Original search:
"Mutations in the adenosine deaminase ADAR1 that prevent endogenous Z-RNA binding induce Aicardi-Goutières-syndrome-like encephalopathy," was published inImmunityat DOI:https://doi.
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