期刊
EMBO JOURNAL
卷 34, 期 1, 页码 97-114出版社
WILEY
DOI: 10.15252/embj.201488979
关键词
cartwheel; centriole; centrosome; chromosome segregation; genome integrity
资金
- JSPS Fellows
- Ministry of Education, Science, Sports and Culture of Japan
- Improvement of Research environment for young researchers
- JST
- Uehara Memorial Foundation
- Takeda Science Foundation
- Mitsubishi foundation
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Astellas Foundation for Research on Metabolic Disorders
- The Sagawa Foundation for Promoting Cancer Research
- Novartis Foundation for the Promotion of Science
- Center for the Promotion of Integrated Sciences of Sokendai
- Transdisciplinary Research Integration center
- Grants-in-Aid for Scientific Research [24687028, 26650080, 24687026, 15H01511] Funding Source: KAKEN
Formation of a new centriole adjacent to a pre-existing centriole occurs only once per cell cycle. Despite being crucial for genome integrity, the mechanisms controlling centriole biogenesis remain elusive. Here, we identify RBM14 as a novel suppressor of assembly of centriolar protein complexes. Depletion of RBM14 in human cells induces ectopic formation of centriolar protein complexes through function of the STIL/CPAP complex. Intriguingly, the formation of such structures seems not to require the cartwheel structure that normally acts as a scaffold for centriole formation, whereas they can retain pericentriolar material and microtubule nucleation activity. Moreover, we find that, upon RBM14 depletion, a part of the ectopic centriolar protein complexes in turn assemble into structures more akin to centrioles, presumably by incorporating HsSAS-6, a cartwheel component, and cause multipolar spindle formation. We further demonstrate that such structures assemble in the cytoplasm even in the presence of pre-existing centrioles. This study sheds light on the possibility that ectopic formation of aberrant structures related to centrioles may contribute to genome instability and tumorigenesis.
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