Graded requirement for the spliceosome in cell cycle progression

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

Research output: Contribution to journalArticle

9 Citations (Scopus)

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

Fingerprint

Spliceosomes
Cell Cycle
G1 Phase Cell Cycle Checkpoints
Genomic Instability
Mitosis
DNA Damage
Genome
Phenotype
Gene Expression
Messenger RNA

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

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

Graded requirement for the spliceosome in cell cycle progression. / Karamysheva, Zemfira; Díaz-Martínez, Laura A.; Warrington, Ross; Yu, Hongtao.

In: Cell Cycle, Vol. 14, No. 12, 01.01.2015, p. 1873-1883.

Research output: Contribution to journalArticle

Karamysheva, Z, Díaz-Martínez, LA, Warrington, R & Yu, H 2015, 'Graded requirement for the spliceosome in cell cycle progression', Cell Cycle, vol. 14, no. 12, pp. 1873-1883. https://doi.org/10.1080/15384101.2015.1039209
Karamysheva, Zemfira ; Díaz-Martínez, Laura A. ; Warrington, Ross ; Yu, Hongtao. / Graded requirement for the spliceosome in cell cycle progression. In: Cell Cycle. 2015 ; Vol. 14, No. 12. pp. 1873-1883.
@article{3dd1343af5ab429d99f86bd87e503949,
title = "Graded requirement for the spliceosome in cell cycle progression",
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.",
keywords = "Cell cycle, DNA damage, Mitosis, mRNA splicing, Spliceosome",
author = "Zemfira Karamysheva and D{\'i}az-Mart{\'i}nez, {Laura A.} and Ross Warrington and Hongtao Yu",
year = "2015",
month = "1",
day = "1",
doi = "10.1080/15384101.2015.1039209",
language = "English (US)",
volume = "14",
pages = "1873--1883",
journal = "Cell Cycle",
issn = "1538-4101",
publisher = "Landes Bioscience",
number = "12",

}

TY - JOUR

T1 - Graded requirement for the spliceosome in cell cycle progression

AU - Karamysheva, Zemfira

AU - Díaz-Martínez, Laura A.

AU - Warrington, Ross

AU - Yu, Hongtao

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

KW - Cell cycle

KW - DNA damage

KW - Mitosis

KW - mRNA splicing

KW - Spliceosome

UR - http://www.scopus.com/inward/record.url?scp=84943263746&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84943263746&partnerID=8YFLogxK

U2 - 10.1080/15384101.2015.1039209

DO - 10.1080/15384101.2015.1039209

M3 - Article

C2 - 25892155

AN - SCOPUS:84943263746

VL - 14

SP - 1873

EP - 1883

JO - Cell Cycle

JF - Cell Cycle

SN - 1538-4101

IS - 12

ER -