Potent inhibitors of the human RNA ligase Rlig1 highlights its role in RNA integrity maintenance under oxidative cellular stress.

ABSTRACT: Human RNA ligase 1 (Rlig1) catalyzes the ligation of 5'-phosphate to 3'-hydroxyl ends via a conserved three-step mechanism. Rlig1-deficient HEK293 cells exhibit reduced cell viability and RNA integrity under oxidative stress, suggesting Rlig1's role in RNA repair maintenance. Reactive oxygen species (ROS) are linked to various diseases, including neurodegenerative disorders and cancer, where RNA damage has significant effects. This study identifies and characterizes Rlig1 inhibitors to elucidate its role in RNA metabolism. We developed a fluorescence resonance energy transfer (FRET)-based assay to monitor RNA ligation and screened a library of 13 026 bioactive small molecules. SGI-1027 emerged as a promising lead compound, and structure-activity relationship (SAR) studies revealed t

SUBMITTER: Schlor LA 

PROVIDER: S-EPMC11747885 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature