Regulation of the catalytic function of topoisomerase II alpha through association with RNA.
Topoisomerase IIalpha interacts with numerous nuclear factors, through which it is engaged in diverse nuclear events such as DNA replication, transcription and the formation or maintenance of heterochromatin. We previously reported that topoisomerase IIalpha interacts with RNA helicase A (RHA), consistent with a recent view that topoisomerases and helicases function together. Intrigued by our observation that the RHA-topoisomerase IIalpha interaction is sensitive to ribonuclease A, we explored whether the RHA-topoisomerase IIalpha interaction can be recapitulated in vitro using purified proteins and a synthetic RNA. This work led us to an unexpected finding that an RNA-binding activity is intrinsically associated with topoisomerase IIalpha. Topoisomerase IIalpha stably interacted with RNA harboring a 3'-hydroxyl group but not with RNA possessing a 3'-phosphate group. When measured in decatenation and relaxation assays, RNA binding influenced the catalytic function of topoisomerase IIalpha to regulate DNA topology. We discuss a possible interaction of topoisomerase IIalpha with the poly(A) tail and G/U-rich 3'-untranslated region (3'-UTR) of mRNA as a key step in transcription termination.
Park
Seung-Won
SW
Department of Biochemistry and Molecular Biology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, Newark, NJ 07103, USA.
Parrott
Andrew M
AM
Fritz
David T
DT
Park
Yongkyu
Y
Mathews
Michael B
MB
Lee
Chee-Gun
CG
D000951:Antigens, Neoplasm / Q000378:metabolism*; D002384:Catalysis; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D012313:RNA / Q000378:metabolism*; D020365:RNA Helicases / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D016601:RNA-Binding Proteins; D012313:RNA; D020365:RNA Helicases; D004250:DNA Topoisomerases, Type II