Genetically targeted mTORC1 inhibitor reveals transcriptional control by nuclear mTORC1.

Targeting TerminaTOR to the nucleus specifically inhibits nuclear mTORC1 and reveals that nuclear mTORC1 regulates transcription of CCAAT motif-containing genes.

• Why it matters: mTORC1 is known to act at multiple subcellular locations, but the specific functions and compartment-specific signaling roles remain unclear.
• What they did: The study developed TerminaTOR, a genetically encodable mTORC1 inhibitor that can be targeted to subcellular compartments, including the lysosome and nucleus.
• The result: Nuclear-targeted TerminaTOR inhibits nuclear mTORC1 and uncovers noncanonical control of CCAAT motif-containing gene transcription, while lysosome targeting blocks lysosomal mTORC1 and induces autophagy.

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