Graded requirement for the spliceosome in cell cycle progression

Zemfira Karamysheva, Laura A. Díaz-Martínez, Ross Warrington, Hongtao Yu

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Genome stability is ensured by multiple surveillance mechanisms that monitor the duplication, segregation, and integrity of the genome throughout the cell cycle. Depletion of components of the spliceosome, a macromolecular machine essential for mRNA maturation and gene expression, has been associated with increased DNA damage and cell cycle defects. However, the specific role for the spliceosome in these processes has remained elusive, as different cell cycle defects have been reported depending on the specific spliceosome subunit depleted. Through a detailed cell cycle analysis after spliceosome depletion, we demonstrate that the spliceosome is required for progression through multiple phases of the cell cycle. Strikingly, the specific cell cycle phenotype observed after spliceosome depletion correlates with the extent of depletion. Partial depletion of a core spliceosome component results in defects at later stages of the cell cycle (G2 and mitosis), whereas a more complete depletion of the same component elicits an early cell cycle arrest in G1. We propose a quantitative model in which different functional dosages of the spliceosome are required for different cell cycle transitions.

Original languageEnglish (US)
Pages (from-to)1873-1883
Number of pages11
JournalCell Cycle
Volume14
Issue number12
DOIs
StatePublished - Jan 1 2015

Keywords

  • Cell cycle
  • DNA damage
  • Mitosis
  • Spliceosome
  • mRNA splicing

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Karamysheva, Z., Díaz-Martínez, L. A., Warrington, R., & Yu, H. (2015). Graded requirement for the spliceosome in cell cycle progression. Cell Cycle, 14(12), 1873-1883. https://doi.org/10.1080/15384101.2015.1039209