title: Stable pausing by RNA polymerase II provides an opportunity to target and integrate regulatory signals.
abstract: Metazoan gene expression is often regulated after the recruitment of RNA polymerase II (Pol II) to promoters, through the controlled release of promoter-proximally paused Pol II into productive RNA synthesis. Despite the prevalence of paused Pol II, very little is known about the dynamics of these early elongation complexes or the fate of the short transcription start site-associated (tss) RNAs they produce. Here, we demonstrate that paused elongation complexes can be remarkably stable, with half-lives exceeding 15 min at genes with inefficient pause release. Promoter-proximal termination by Pol II is infrequent, and released tssRNAs are targeted for rapid degradation. Further, we provide evidence that the predominant tssRNA species observed are nascent RNAs held within early elongation complexes. We propose that stable pausing of polymerase provides a temporal window of opportunity for recruitment of factors to modulate gene expression and that the nascent tssRNA represents an appealing target for these interactions.
authors.affiliation: Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
authors.forename: Telmo
authors.initials: T
authors.lastname: Henriques
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Gilchrist
authors.forename: Sergei
authors.initials: S
authors.lastname: Nechaev
authors.forename: Michael
authors.initials: M
authors.lastname: Bern
authors.forename: Ginger W
authors.initials: GW
authors.lastname: Muse
authors.forename: Adam
authors.initials: A
authors.lastname: Burkholder
authors.forename: David C
authors.initials: DC
authors.lastname: Fargo
authors.forename: Karen
authors.initials: K
authors.lastname: Adelman
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster; D063326:Exosome Multienzyme Ribonuclease Complex / Q000378:metabolism; D005786:Gene Expression Regulation; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000502:physiology*; D020871:RNA Stability; D020733:RNA, Small Cytoplasmic / Q000378:metabolism*; D015398:Signal Transduction; D061805:Transcription Elongation, Genetic
chemical_list: D002843:Chromatin; D029721:Drosophila Proteins; D020733:RNA, Small Cytoplasmic; D012319:RNA Polymerase II; D063326:Exosome Multienzyme Ribonuclease Complex