RNA Interacts with Topoisomerase I to Modulate its Catalytic Activity

Topoisomerase I (TOP1) is an essential enzyme that relaxes DNA to prevent and dissipate torsional stress during transcription. However, the mechanisms underlying the regulation of TOP1 activity remain elusive. Using eCLIP and UV-RIP-seq we identify TOP1 as a RNA binding protein (RBP). Using a TOP1 RNA binding mutant and TOP1cc-seq to map TOP1 catalytic activity, we reveal that RNA opposes TOP1 activity as RNAPII commences transcription of active genes. These findings support new insights into the coordinated actions of RNA and TOP1 in regulating DNA topological stress intrinsic to RNAPII-dependent transcription. Examination of TOP1 UV-RIP-seq, TOP1 eCLIP-seq and TOP1cc-seq in SW480 colon cancer cell line.