mTOR inactivation governs adaptive survival to ribosome biogenesis deficiency.

Inhibition of RNA polymerase I reveals that mTOR inactivation enables survival despite severe translational suppression, by reallocating limited ribosomes toward survival-essential transcripts.

• Why it matters: Cancer cells with high metabolic activity must adapt to loss of translational capacity, yet the survival mechanisms under ribosome biogenesis defects are unclear for therapy design.
• What they did: Functional genomics screens during RNA polymerase I inhibition identified mTOR inactivation; mTORC1 inhibition did not restore rRNA synthesis or ribosome biogenesis, but shifted ribosome allocation from highly translated 5'TOP mRNAs.
• The result: This “translational fitness” model implies mTOR-driven prioritization of translational resources is a minimal requirement for cell survival when translation is compromised, informing translation-regulation targeting in cancer therapy.

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