The human RNA polymerase II-associated factor 1 (hPaf1): A new regulator of cell-cycle progression

Nicolas Moniaux, Christophe Nemos, Shonali Deb, Bing Zhu, Irena Dornreiter, Michael A Hollingsworth, Surinder Kumar Batra

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: The human PAF (hPAF) complex is part of the RNA polymerase II transcription apparatus and regulates multiple steps in gene expression. Further, the yeast homolog of hPaf1 has a role in regulating the expression of a subset of genes involved in the cell-cycle. We therefore investigated the role of hPaf1 during progression of the cell-cycle. Methodology/Findings: Herein, we report that the expression of hPaf1, a subunit of the hPAF complex, increases with cell-cycle progression and is regulated in a cell-cycle dependant manner. hPaf1 specifically regulates a subclass of genes directly implicated in cell-cycle progression during G1/S, S/G2, and G2/M. In prophase, hPaf1 aligns in filament-like structures, whereas in metaphase it is present within the pole forming a crown-like structure, surrounding the centrosomes. Moreover, hPaf1 is degraded during the metaphase to anaphase transition. In the nucleus, hPaf1 regulates the expression of cyclins A1, A2, D1, E1, B1, and Cdk1. In addition, expression of hPaf1 delays DNA replication but favors the G2/M transition, in part through microtubule assembly and mitotic spindle formation. Conclusion/Significance: Our results identify hPaf1 and the hPAF complex as key regulators of cell-cycle progression. Mutation or loss of stoichiometry of at least one of the members may potentially lead to cancer development.

Original languageEnglish (US)
Article numbere7077
JournalPloS one
Volume4
Issue number9
DOIs
StatePublished - Sep 22 2009

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RNA Polymerase II
DNA-directed RNA polymerase
cell cycle
Cell Cycle
Cells
Metaphase
Cyclin A1
metaphase
Genes
Cyclin A2
Prophase
centrosomes
Transcription
gene expression
Centrosome
Anaphase
mitotic spindle apparatus
Spindle Apparatus
Gene expression
Stoichiometry

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

The human RNA polymerase II-associated factor 1 (hPaf1) : A new regulator of cell-cycle progression. / Moniaux, Nicolas; Nemos, Christophe; Deb, Shonali; Zhu, Bing; Dornreiter, Irena; Hollingsworth, Michael A; Batra, Surinder Kumar.

In: PloS one, Vol. 4, No. 9, e7077, 22.09.2009.

Research output: Contribution to journalArticle

Moniaux, Nicolas ; Nemos, Christophe ; Deb, Shonali ; Zhu, Bing ; Dornreiter, Irena ; Hollingsworth, Michael A ; Batra, Surinder Kumar. / The human RNA polymerase II-associated factor 1 (hPaf1) : A new regulator of cell-cycle progression. In: PloS one. 2009 ; Vol. 4, No. 9.
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