We present a molecular dissection of pause site-dependent transcriptional termination for mammalian RNA polymerase II (Pol II)-transcribed genes. We show that nascent transcripts form RNA/DNA hybrid structures (R-loops) behind elongating Pol II and are especially prevalent over G-rich pause sites positioned downstream of gene poly(A) signals. Senataxin, a helicase protein associated with AOA2/ALS4 neurodegenerative disorders, acts to resolve these R-loop structures and by so doing allows access of the 5. '-3. ' exonuclease Xrn2 at 3. ' cleavage poly(A) sites. This affords 3. ' transcript degradation and consequent Pol II termination. In effect, R-loops formed over G-rich pause sites, followed by their resolution by senataxin, are key steps in the termination process. © 2011 Elsevier Inc.
Skourti-Stathaki, K., Proudfoot, N. J., & Gromak, N. (2011). Human Senataxin Resolves RNA/DNA Hybrids Formed at Transcriptional Pause Sites to Promote Xrn2-Dependent Termination. Molecular Cell, 42(6), 794–805. https://doi.org/10.1016/j.molcel.2011.04.026