Zinc-dependent RNA-binding protein controls hepatocyte senescence and recovery from alcohol-related liver failure.

ZFP36L1, a zinc-dependent RNA-binding protein, suppresses hepatocyte senescence and ALD progression by destabilizing p21 and JAG1 mRNAs in mice and humans.

• Why it matters: Understanding why some individuals recover from alcohol-related liver disease while others develop liver failure remains unclear, partly due to limited knowledge of molecular regulators of hepatocyte fate and senescence.
• What they did: Researchers deleted ZFP36L1 in mouse hepatocytes and analyzed human liver samples, examining its role in ALD, transcriptional changes, senescence, and zinc-dependent regulation, focusing on its mRNA targets.
• The result: Loss of ZFP36L1 worsened ALD, increased hepatocyte senescence, and activated inflammatory pathways, with activity declining alongside disease severity and zinc signaling, suggesting ZFP36L1 as a potential therapeutic target.