Acetylation of microtubule-binding PinX1 orchestrates ribosome biogenesis to nutrient starvation via the RNA polymerase I preinitiation complex

The shutdown of ribosome biogenesis is one of the sophisticated strategies for cells to save energy in response to nutrient starvation. However, the mechanism orchestrating ribosome biogenesis with cellular nutrition status remains unclear. Here, we identified the role of PIN2/TRF1-interacting telomerase inhibitor 1 (PinX1) in regulating ribosome biogenesis. PinX1 is highly expressed in colorectal cancers (CRC). Depletion of PinX1 impairs rDNA transcription, compromises ribosome biogenesis and inhibits tumor cells proliferation. Mechanically, associated with UBTF, PinX1 directly binds to RNA polymerase I subunit G (POLR1G) which is required for the assembly of RNA polymerase I preinitiation complex (PIC). Upon nutrient starvation, PinX1 is acetylated at K43, K133, K140, K149, K190, K222, which hinders its binding to POLR1G leading to disassembly of PIC. Collectively, our findings uncover a novel role of PinX1 and its acetylation, fine-tuning nucleolar transcription to stress signaling.