title: Distinct mechanisms for repression of RNA polymerase III transcription by the retinoblastoma tumor suppressor protein.
abstract: The retinoblastoma (RB) protein represses global RNA polymerase III transcription of genes that encode nontranslated RNAs, potentially to control cell growth. However, RNA polymerase III-transcribed genes exhibit diverse promoter structures and factor requirements for transcription, and a universal mechanism explaining global repression is uncertain. We show that RB represses different classes of RNA polymerase III-transcribed genes via distinct mechanisms. Repression of human U6 snRNA (class 3) gene transcription occurs through stable promoter occupancy by RB, whereas repression of adenovirus VAI (class 2) gene transcription occurs in the absence of detectable RB-promoter association. Endogenous RB binds to a human U6 snRNA gene in both normal and cancer cells that maintain functional RB but not in HeLa cells whose RB function is disrupted by the papillomavirus E7 protein. Both U6 promoter association and transcriptional repression require the A/B pocket domain and C region of RB. These regions of RB contribute to U6 promoter targeting through numerous interactions with components of the U6 general transcription machinery, including SNAP(C) and TFIIIB. Importantly, RB also concurrently occupies a U6 promoter with RNA polymerase III during repression. These observations suggest a novel mechanism for RB function wherein RB can repress U6 transcription at critical steps subsequent to RNA polymerase III recruitment.
authors.affiliation: Program in Cell and Molecular Biology, Michigan State University, East Lansing 48824, USA.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Hirsch
authors.forename: Gauri W
authors.initials: GW
authors.lastname: Jawdekar
authors.forename: Kang-Ae
authors.initials: KA
authors.lastname: Lee
authors.forename: Liping
authors.initials: L
authors.lastname: Gu
authors.forename: R William
authors.initials: RW
authors.lastname: Henry
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D046911:Macromolecular Substances; D011401:Promoter Regions, Genetic; D012320:RNA Polymerase III / Q000096:biosynthesis / Q000235:genetics*; D012342:RNA, Small Nuclear / Q000235:genetics; D016160:Retinoblastoma Protein / Q000502:physiology*; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000502:physiology
chemical_list: D046911:Macromolecular Substances; D012342:RNA, Small Nuclear; D016160:Retinoblastoma Protein; D025521:Tumor Suppressor Proteins; C405486:U6 small nuclear RNA; D012320:RNA Polymerase III