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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.

Original publication

DOI

10.1016/j.molcel.2011.04.026

Type

Journal article

Journal

Mol Cell

Publication Date

24/06/2011

Volume

42

Pages

794 - 805

Keywords

Cells, Cultured, DNA, Exoribonucleases, HeLa Cells, Humans, Nucleic Acid Heteroduplexes, Nucleic Acid Hybridization, RNA, RNA Helicases, Transcription, Genetic