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

Topoisomerase II 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 II interacts with RNA helicase A (RHA), consistent with a recent view that topoisomerases and helicases function together. Intrigued by our observation that the RHAtopoisomerase II interaction is sensitive to ribonuclease A, we explored whether the RHAtopoisomerase II 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 II. Topoisomerase II 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 II to regulate DNA topology. We discuss a possible interaction of topoisomerase II with the poly(A) tail and G/U-rich 3-untranslated region (3-UTR) of mRNA as a key step in transcription termination.