BCCIP is required for nucleolar recruitment of eIF6 and 12S pre-rRNA production during 60S ribosome biogenesis

Author:

Ye Caiyong1,Liu Bochao1,Lu Huimei1,Liu Jingmei1,Rabson Arnold B2,Jacinto Estela3,Pestov Dimitri G4ORCID,Shen Zhiyuan1ORCID

Affiliation:

1. Rutgers Cancer Institute of New Jersey, Department of Radiation Oncology, Rutgers Robert Wood Johnson Medical School, 195 Little Albany Street, New Brunswick, NJ 08901, USA

2. Department of Pharmacology, and The Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA

3. Department of Biochemistry and Molecular Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, USA

4. Department of Cell Biology and Neuroscience, Rowan University School of Osteopathic Medicine, Stratford, NJ, USA

Abstract

Abstract 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 eIF6 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.

Funder

NIH

Rutgers Cancer Institute of New Jersey

Robert Wood Johnson Foundation

Publisher

Oxford University Press (OUP)

Subject

Genetics

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