Adar contributes to genome integrity by regulating R-loop homeostasis in Drosophila

Area of Science:

• Molecular Biology
• Epigenetics
• Genomics

Background:

• Adenosine deaminase acting on RNA (Adar) is crucial for RNA editing.
• Its broader biological roles and regulatory mechanisms are not well understood.

Purpose of the Study:

• Investigate the function of Adar beyond its RNA editing role.
• Determine Adar's involvement in maintaining genome stability.

Main Methods:

• Utilized Drosophila as a model organism.
• Performed genome-wide ssDRIP-seq to detect R-loop accumulation.
• Assessed the impact of RNase H1 (RNH1) overexpression and catalytically inactive Adar mutants.

Main Results:

• Adar deficiency in Drosophila resulted in genome instability, DNA damage, and mitotic defects.
• Loss of Adar led to global R-loop accumulation, especially at promoters, introns, and repetitive elements.
• RNase H1 overexpression rescued genome instability, and a catalytically inactive Adar mutant suppressed R-loops and maintained genome integrity.

Conclusions:

• Adar plays an essential, editing-independent role in genome stability by regulating R-loop homeostasis.
• This study reveals conserved Adar functions beyond RNA editing.
• Drosophila serves as a valuable model for studying R-loop-mediated genomic instability.