Human Puf-A, a Novel Component of 90S Pre-ribosome, Links Ribosome Biogenesis to Cancer Progression

Yu, J.; Cho, H.-C.; Huang, Y.; Hung, J.-T.; Lai, L.-C.; Wang, S.-H.; Liu, Y.-H.; Cho, I.-M.; Kuo, M.-W.; Cheng, P.-Y.; Ho, M.-Y.; Lin, R.-J.; Yu, A. L.

doi:10.1101/281857

bioRxiv · 10.1101/281857

Human Puf-A, a Novel Component of 90S Pre-ribosome, Links Ribosome Biogenesis to Cancer Progression

Yu, J.·Cho, H.-C.·Huang, Y.·Hung, J.-T.·Lai, L.-C.·Wang, S.-H.·Liu, Y.-H.·Cho, I.-M.·Kuo, M.-W.·Cheng, P.-Y.·Ho, M.-Y.·Lin, R.-J.·Yu, A. L.

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Abstract

We describe a novel biogenesis factor of the 90S pre-ribosome, Puf-A, which is a negative transcriptional target of p53. The expression of Puf-A is not only upregulated in advanced human lung cancer and tumors of patients especially with TP53 mutation, but also is highly prognostic for stage I lung cancer. Loss of Puf-A expression prevents KrasG12D/p53-/--induced tumor progression in the lungs and induces apoptosis in TP53- mutated cancers and c-Myc/p53-/--transformed cells as well. Overexpression of Puf-A enhances proliferation of normal cells after c-Myc induction and overcomes the cell-cycle checkpoints incurred by p53 expression. Mechanistically, Puf-A interacts with double-stranded structures of the 5.8S sequence within pre-rRNA and maintains the integrity of 90S pre-ribosomes, thereby impacting early ribosome assembly and export of ribosomes from nuclei. Silencing of Puf-A disrupts the assembly of 90S pre-ribosomes and induces the translocation of its associated nucleophosmin (NPM1) from nucleoli to the nucleoplasm, resulting in impairment of ribosome synthesis. Thus, Puf-A is crucial for over-activation of ribosome biogenesis and contributes to tumor progression and cancer growth.

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Yu, J., Cho, H.-C., Huang, Y., Hung, J.-T., Lai, L.-C., Wang, S.-H., Liu, Y.-H., Cho, I.-M., Kuo, M.-W., Cheng, P.-Y., Ho, M.-Y., Lin, R.-J., Yu, A. L.. 2018-03-13. Human Puf-A, a Novel Component of 90S Pre-ribosome, Links Ribosome Biogenesis to Cancer Progression. https://doi.org/10.1101/281857

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