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The ATPase hCINAP regulates 18S rRNA processing and is essential for embryogenesis and tumour growth

Article scientifique 2016 Anglais

Résumé

Dysfunctions in ribosome biogenesis cause developmental defects and increased cancer susceptibility; however, the connection between ribosome assembly and tumorigenesis remains unestablished. Here we show that hCINAP (also named AK6) is required for human 18S rRNA processing and 40S subunit assembly. Homozygous CINAP(-/-) mice show embryonic lethality. The heterozygotes are viable and show defects in 18S rRNA processing, whereas no delayed cell growth is observed. However, during rapid growth, CINAP haploinsufficiency impairs protein synthesis. Consistently, hCINAP depletion in fast-growing cancer cells inhibits ribosome assembly and abolishes tumorigenesis. These data demonstrate that hCINAP reduction is a specific rate-limiting controller during rapid growth. Notably, hCINAP is highly expressed in cancers and correlated with a worse prognosis. Genome-wide polysome profiling shows that hCINAP selectively modulates cancer-associated translatome to promote malignancy. Our results connect the role of hCINAP in ribosome assembly with tumorigenesis. Modulation of hCINAP expression may be a promising target for cancer therapy.

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Bai, D., Zhang, J., Li, T., Hang, R., Liu, Y., Tian, Y., Huang, D., Qu, L., Cao, X., Ji, J., Zheng, X. (2016). The ATPase hCINAP regulates 18S rRNA processing and is essential for embryogenesis and tumour growth. https://doi.org/10.1038/ncomms12310

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Auteur(s)

Dongmei Bai Jinfang Zhang Tingting Li Runlai Hang Yong Liu Yonglu Tian Dadu Huang Linglong Qu Xiaofeng Cao Jiafu Ji Xiaofeng Zheng

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