MATRIN3 deficiency in human cells triggers an autoinflammatory response via cGAS-STING activation.

MATRIN3 deficiency in human cells activates the cGAS-STING pathway, triggering an autoinflammatory response and upregulating interferon-stimulated genes.

• Why it matters: Understanding how MATR3 maintains cellular health is crucial because its loss leads to immune activation and may underlie neurodegenerative diseases, highlighting a significant disease mechanism.
• What they did: Researchers used gene editing to create MATR3-deficient human iPSCs and HAP1 cells, then employed RNA sequencing and PAR-CLIP to identify molecular changes and direct targets affected by MATR3 loss.
• The result: Loss of MATR3 caused defective RNA processing, accumulation of cytoplasmic RNA-DNA hybrids, and activation of innate immune signaling, revealing new pathways involved in disease and potential therapeutic targets.