Keeping immunostimulatory self-RNA under the rADAR

Article Multidisciplinary Sciences

ADAR1 mutation causes ZBP1-dependent immunopathology

Nicholas W. Hubbard et al.

Summary: The RNA-editing enzyme ADAR1 inhibits innate immune activation and pathology by disrupting the duplex structure of endogenous double-stranded RNA species. Alteration of the Z-DNA-binding domain (ZBD) of ADAR1 leads to activation of ZBP1, causing autoinflammatory pathology.

NATURE (2022)

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Article Multidisciplinary Sciences

ADAR1 averts fatal type I interferon induction by ZBP1

Huipeng Jiao et al.

Summary: Mutations of the ADAR1 gene cause chronic activation of type I interferon responses, leading to severe diseases. The interaction between ADAR1 and another protein called ZBP1 prevents IFN activation. Deficiency or mutation of ZBP1's Z alpha domains reduces expression of IFN-stimulated genes and prevents early postnatal lethality in mice with mutated ADAR1 Z alpha domain.

NATURE (2022)

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Article Multidisciplinary Sciences

ADAR1 prevents autoinflammation by suppressing spontaneous ZBP1 activation

Richard de Reuver et al.

Summary: The RNA-editing enzyme ADAR1 plays an important role in limiting the accumulation of immunostimulatory dsRNA. Reduced ADAR1 activity can lead to severe inflammatory diseases, while complete loss of ADAR1 activity is embryonically lethal and causes autoinflammation. ADAR1 not only prevents overactivation of MDA5 and PKR, but also inhibits the spontaneous activation of ZBP1.

NATURE (2022)

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Article Biochemistry & Molecular Biology