RBM14 prevents assembly of centriolar protein complexes and maintains mitotic spindle integrity

EMBO J. 2015 Jan 2;34(1):97-114. doi: 10.15252/embj.201488979. Epub 2014 Nov 10.

Abstract

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.

Keywords: cartwheel; centriole; centrosome; chromosome segregation; genome integrity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Centrioles / metabolism*
  • Genomic Instability / genetics
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / genetics
  • Microtubules / metabolism*
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism*

Substances

  • CENPJ protein, human
  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • Microtubule-Associated Proteins
  • Multiprotein Complexes
  • RBM14 protein, human
  • SASS6 protein, human