WBP11 is required for splicing the TUBGCP6 pre-mRNA to promote centriole duplication

J Cell Biol. 2020 Jan 6;219(1):e201904203. doi: 10.1083/jcb.201904203.

Abstract

Centriole duplication occurs once in each cell cycle to maintain centrosome number. A previous genome-wide screen revealed that depletion of 14 RNA splicing factors leads to a specific defect in centriole duplication, but the cause of this deficit remains unknown. Here, we identified an additional pre-mRNA splicing factor, WBP11, as a novel protein required for centriole duplication. Loss of WBP11 results in the retention of ∼200 introns, including multiple introns in TUBGCP6, a central component of the γ-TuRC. WBP11 depletion causes centriole duplication defects, in part by causing a rapid decline in the level of TUBGCP6. Several additional splicing factors that are required for centriole duplication interact with WBP11 and are required for TUBGCP6 expression. These findings provide insight into how the loss of a subset of splicing factors leads to a failure of centriole duplication. This may have clinical implications because mutations in some spliceosome proteins cause microcephaly and/or growth retardation, phenotypes that are strongly linked to centriole defects.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle
  • Centrioles / genetics*
  • Centrosome / physiology
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • HCT116 Cells
  • HeLa Cells
  • Humans
  • Introns
  • Microtubule-Associated Proteins / genetics*
  • Mitosis
  • Nuclear Receptor Coactivators / genetics
  • Nuclear Receptor Coactivators / metabolism
  • RNA Precursors / genetics*
  • RNA Splicing / genetics*
  • RNA Splicing Factors / genetics
  • RNA Splicing Factors / metabolism*
  • RNA, Messenger / genetics*
  • Transcriptome

Substances

  • DNA-Binding Proteins
  • Microtubule-Associated Proteins
  • Nuclear Receptor Coactivators
  • RNA Precursors
  • RNA Splicing Factors
  • RNA, Messenger
  • SNW1 protein, human
  • TUBGCP6 protein, human
  • WBP11 protein, human