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

• DOI: 10.1038/ncomms12310
• Publication Date: 2016-08-01T12:00:34Z
• Authors: Dongmei Bai; Jinfang Zhang; Tingting Li; Runlai Hang; Yong Liu; Yonglu Tian; Dadu Huang; Linglong Qu; Xiaofeng Cao; Jiafu Ji; Xiaofeng Zheng
• Keywords: ribosome biogenesis; Polysome; Ribosome profiling; Haploinsufficiency

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