Regulation of DNA topoisomerase IIβ through RNA-dependent association with heterogeneous nuclear ribonucleoprotein U (hnRNP U)

Shinji Kawano, Mary Miyaji, Shoko Ichiyasu, Kimiko M. Tsutsui, Ken Tsutsui

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Recent studies suggest that DNA to poisomerase IIβ(topo IIβ) is involved in transcriptional activation of certain genes, which assumes accurate targeting of the enzyme to its action site. The target selection may be achieved by cooperation with unknown regulatory factors. To seek out such factors, we looked for proteins associated with the enzyme in differentiating cerebellar neurons. Antibody against topo IIβ co-precipitated RNA-binding proteins including PSF, NonO/p54nrb, as well as hnRNP U/SAF-A/SP120. Reconstitution experiments with tag-purified proteins showed that topo IIβ associates stoichiometrically with SP120 in the presence of RNA that was co-purified with SP120. The most effective RNA species for the complex formation was a subset of cellular polyadenylated RNAs. The C-terminal 187-residue domain of SP120 was necessary and sufficient for the association with both topo IIβ and the endogenous RNA. The RNA isolated from the tag-purified SP120 inhibited the relaxation of supercoiled DNA by topo IIβ. When the enzyme associates with SP120, however, the inhibition was abolished and the catalytic property was modulated to more processive mode, which may prolong its residence time at the genomic target site. Furthermore, the presence of SP120 was required for the stable expression of topo IIβ in vivo. Thus, SP120 regulates the enzyme in dual ways.

Original languageEnglish
Pages (from-to)26451-26460
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number34
DOIs
Publication statusPublished - Aug 20 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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