期刊
NUCLEIC ACIDS RESEARCH
卷 48, 期 22, 页码 12817-12832出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkaa1114
关键词
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资金
- NIH [GM079176, CA154674, R01CA156706, R01CA195612, R03CA246009]
- Histopathology & Imaging and Genome Editing Shared Resources of the Rutgers Cancer Institute of New Jersey [NIH P30CA072720]
- RobertWood Johnson Foundation
Ribosome biogenesis is a fundamental process required for cell proliferation. Although evolutionally conserved, the mammalian ribosome assembly system is more complex than in yeasts. BCCIP was originally identified as a BRCA2 and p21 interacting protein. A partial loss of BCCIP function was sufficient to trigger genomic instability and tumorigenesis. However, a complete deletion of BCCIP arrested cell growth and was lethal in mice. Here, we report that a fraction of mammalian BCCIP localizes in the nucleolus and regulates 60S ribosome biogenesis. Both abrogation of BCCIP nucleolar localization and impaired BCCIP-eIF6 interaction can compromise elF6 recruitment to the nucleolus and 60S ribosome biogenesis. BCCIP is vital for a pre-rRNA processing step that produces 12S pre-rRNA, a precursor to the 5.8S rRNA. However, a heterozygous Bccip loss was insufficient to impair 60S biogenesis in mouse embryo fibroblasts, but a profound reduction of BCCIP was required to abrogate its function in 60S biogenesis. These results suggest that BCCIP is a critical factor for mammalian pre-rRNA processing and 60S generation and offer an explanation as to why a subtle dysfunction of BCCIP can be tumorigenic but a complete depletion of BCCIP is lethal.
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