Human senataxin uses distinct peripheral elements to unwind R-loops and act on RNA polymerase II

SETX helicase domain uses distinct peripheral elements to unwind R-loops and regulate mammalian RNAPII, with CT-RBD required for R-loop unwinding and prong subdomain required for RNAPII outcomes.

• Why it matters: Persistent R-loops and stalled RNAPII elongation complexes threaten genome stability, but it has been unclear whether SETX’s R-loop resolution and RNAPII regulation depend on the same molecular features.
• What they did: The authors used cryo-EM to map the conserved SETX-HD helicase core and RNA-binding channel, then performed biochemical and reconstituted mammalian transcription assays to test roles of the CT-RBD and the prong subdomain.
• The result: CT-RBD stabilizes RNA engagement and is required for efficient R-loop unwinding, while CT-RBD deletion preserves RNAPII-associated activities; conversely, swapping the prong for fungal Sen1 preserves R-loop unwinding but impairs both RNAPII outcomes.

AI summary of the abstract · may contain errors · not medical advice · read the paper.