Structural and mechanistic basis of ADAR1-mediated RNA editing and immune regulation

TL;DR

This paper reviews how ADAR1 edits RNA and regulates the immune system, focusing on its structure and function.

Contribution

The paper integrates recent structural and mechanistic findings to clarify ADAR1's role in RNA editing and immune regulation.

Findings

ADAR1's multi-domain architecture contributes to dsRNA substrate engagement and selectivity.

Insights into ADAR1's catalytic mechanism and domain-specific activities refine its role in immune signaling suppression.

Emerging knowledge on ADAR1's RNA substrates and protein interactions reveals principles underlying its regulatory functions.

Abstract

Adenosine deaminase acting on RNA 1 (ADAR1) is a central regulator of innate immunity. By binding to and catalyzing adenosine-to-inosine deamination within double-stranded RNAs, ADAR1 mitigates the immunogenicity of self-derived RNAs and preserves cellular homeostasis. In this review, we summarize recent structural and mechanistic advances that illuminate key features of ADAR1 architecture, including how its multi-domains engage dsRNA substrates and contribute to substrate selectivity. Integrated with decades of biochemical and genetic studies, these insights refine our understanding of ADAR1's catalytic mechanism, domain-specific activities, and roles in suppressing immune signaling. We further highlight emerging knowledge on ADAR1's RNA substrate landscape, its interactions with protein partners, and the mechanistic principles that underlie its broad RNA editing and immune regulatory functions, with implications for disease pathogenesis and therapeutic RNA editing.

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