title: 5,6-Dichloro-1-beta-D-ribofuranosylbenzimidazole inhibits transcription elongation by RNA polymerase II in vitro.
abstract: The purine nucleoside analog 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) is a selective inhibitor of transcription by RNA polymerase II. Although a wealth of in vivo studies have suggested that DRB inhibits transcription by enhancing the premature termination of elongating polymerase molecules, in vitro studies to date have been interpreted to suggest that DRB acts at the level of transcription initiation. We have analyzed the mechanism of DRB-mediated transcription inhibition in vitro both in HeLa whole cell extracts and in a partially purified transcription system. The results indicate that the extent to which DRB inhibits the synthesis of a RNA transcript is directly proportional to its length. For example, DRB was found to preferentially inhibit transcription in vitro of promoter-distal relative to promoter-proximal portions of the adenovirus major late transcription unit. A factor potentially involved in mediating this inhibitory effect is identified. We conclude that the mechanism of DRB inhibition of transcription in vivo and in vitro are similar.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
authors.forename: L A
authors.initials: LA
authors.lastname: Chodosh
authors.forename: A
authors.initials: A
authors.lastname: Fire
authors.forename: M
authors.initials: M
authors.lastname: Samuels
authors.forename: P A
authors.initials: PA
authors.lastname: Sharp
mesh_terms: D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology*; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012319:RNA Polymerase II / Q000037:antagonists & inhibitors*; D012263:Ribonucleosides / Q000494:pharmacology*; D012265:Ribonucleotides / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism; D013698:Templates, Genetic; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D012263:Ribonucleosides; D012265:Ribonucleotides; D012269:Ribosomal Proteins; D004004:Dichlororibofuranosylbenzimidazole; D012319:RNA Polymerase II