Hypoxic Stress Induces LARP1-Driven Stress Granules That Protect mRNAs from Decay to Sustain Mitotic Cell Cycle Progression

Hypoxia induces LARP1-driven stress granules in solid-tumour hypoxia conditions, assembling via the HIF1-REDD1-mTORCC1-4EBP1 axis despite ongoing translation.

• Why it matters: Stress granules are seen in hypoxia, but their assembly logic and whether they actively regulate hypoxic gene expression were unclear.
• What they did: The study tested hypoxia versus arsenite stress granule formation, using pathway dependence on HIF1-REDD1-mTORCC1-4EBP1 and identifying LARP1 as promoting G3BP-dependent assembly specifically during hypoxia. Single-molecule FISH and transcriptomics assessed RNA partitioning and mRNA decay protection.
• The result: mRNAs sequestered in hypoxia SGs show enhanced protein expression and are protected from decay, sustaining a gene-expression program enriched for MCM complex and mitotic cell-cycle regulators; disrupting hypoxia SGs reduces mitotic progression and proliferative competence during prolonged hypoxia.

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