RBM14 prevents assembly of centriolar protein complexes and maintains mitotic spindle integrity.
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.
Centrosome Biology Laboratory, Center for Frontier Research, National Institute of Genetics, Mishima Shizuoka, Japan.
Gen
G
Shiratsuchi
Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, Suita Osaka, Japan.
Katsuyoshi
K
Takaoka
Centrosome Biology Laboratory, Center for Frontier Research, National Institute of Genetics, Mishima Shizuoka, Japan.
Tomoko
T
Ashikawa
Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, Suita Osaka, Japan.
Hiroshi
H
Hamada
Centrosome Biology Laboratory, Center for Frontier Research, National Institute of Genetics, Mishima Shizuoka, Japan dkitagaw@nig.ac.jp.
Daiju
D
Kitagawa
D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002502:Centrioles / Q000378:metabolism*; D042822:Genomic Instability / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*
C414735:CENPJ protein, human; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; C436317:RBM14 protein, human; C497202:SASS6 protein, human
cartwheel; centriole; centrosome; chromosome segregation; genome integrity