title: The ATPase hCINAP regulates 18S rRNA processing and is essential for embryogenesis and tumour growth.
abstract: 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.
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.|Department of Biochemistry and Molecular Biology, School of Life Sciences, Peking University, Yiheyuan Road No. 5, Beijing 100871, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Bai
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.|Department of Biochemistry and Molecular Biology, School of Life Sciences, Peking University, Yiheyuan Road No. 5, Beijing 100871, China.
authors.forename: Jinfang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.|Department of Biochemistry and Molecular Biology, School of Life Sciences, Peking University, Yiheyuan Road No. 5, Beijing 100871, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.affiliation: State key Laboratory of Plant Genetics and National Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.|College of Life Sciences, University of the Chinese Academy of Sciences, Beijing 100039, China.
authors.forename: Runlai
authors.initials: R
authors.lastname: Hang
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.|Department of Biochemistry and Molecular Biology, School of Life Sciences, Peking University, Yiheyuan Road No. 5, Beijing 100871, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Life Sciences, Peking University, Yiheyuan Road No. 5, Beijing 100871, China.
authors.forename: Yonglu
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Life Sciences, Peking University, Yiheyuan Road No. 5, Beijing 100871, China.
authors.forename: Dadu
authors.initials: D
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.|Department of Biochemistry and Molecular Biology, School of Life Sciences, Peking University, Yiheyuan Road No. 5, Beijing 100871, China.
authors.forename: Linglong
authors.initials: L
authors.lastname: Qu
authors.affiliation: State key Laboratory of Plant Genetics and National Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.|College of Life Sciences, University of the Chinese Academy of Sciences, Beijing 100039, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Cao
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Surgery, Peking University Caner Hospital and Institute, Beijing 100142, China.
authors.forename: Jiafu
authors.initials: J
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.|Department of Biochemistry and Molecular Biology, School of Life Sciences, Peking University, Yiheyuan Road No. 5, Beijing 100871, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001940:Breast / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D003106:Colon / Q000473:pathology; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009369:Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011132:Polyribosomes / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D012323:RNA Processing, Post-Transcriptional; D012337:RNA, Ribosomal, 18S / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: C485510:CINAP protein, mouse; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012337:RNA, Ribosomal, 18S; C432963:TSPYL2 protein, human