title: Human senataxin resolves RNA/DNA hybrids formed at transcriptional pause sites to promote Xrn2-dependent termination.
abstract: 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.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Skourti-Stathaki
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Proudfoot
authors.forename: Natalia
authors.initials: N
authors.lastname: Gromak
mesh_terms: D002478:Cells, Cultured; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004265:DNA Helicases; D005095:Exoribonucleases / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D064251:Multifunctional Enzymes; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry; D009693:Nucleic Acid Hybridization; D012313:RNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020365:RNA Helicases / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D064251:Multifunctional Enzymes; D009692:Nucleic Acid Heteroduplexes; D012313:RNA; D004247:DNA; D005095:Exoribonucleases; C120903:XRN2 protein, human; C484368:SETX protein, human; D004265:DNA Helicases; D020365:RNA Helicases