Regulation of the catalytic function of topoisomerase II alpha through association with RNA

Topoisomerase IIα 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 IIα 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 IIα interaction is sensitive to ribonuclease A, we explored whether the RHA-topoisomerase IIα 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 IIα. Topoisomerase IIα 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 IIα to regulate DNA topology. We discuss a possible interaction of topoisomerase IIα with the poly(A) tail and G/U-rich 3′-untranslated region (3′-UTR) of mRNA as a key step in transcription termination.