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Widespread Backtracking by RNA Pol II Is a Major Effector of Gene Activation, 5' Pause Release, Termination, and Transcription Elongation Rate.
Sheridan, Ryan M; Fong, Nova; D'Alessandro, Angelo; Bentley, David L.
Afiliação
  • Sheridan RM; Department Biochemistry and Molecular Genetics, RNA Bioscience Initiative, University of Colorado School of Medicine, Aurora, CO 80045, USA.
  • Fong N; Department Biochemistry and Molecular Genetics, RNA Bioscience Initiative, University of Colorado School of Medicine, Aurora, CO 80045, USA.
  • D'Alessandro A; Department Biochemistry and Molecular Genetics, RNA Bioscience Initiative, University of Colorado School of Medicine, Aurora, CO 80045, USA.
  • Bentley DL; Department Biochemistry and Molecular Genetics, RNA Bioscience Initiative, University of Colorado School of Medicine, Aurora, CO 80045, USA. Electronic address: david.bentley@ucdenver.edu.
Mol Cell ; 73(1): 107-118.e4, 2019 01 03.
Article em En | MEDLINE | ID: mdl-30503775
In addition to phosphodiester bond formation, RNA polymerase II has an RNA endonuclease activity, stimulated by TFIIS, which rescues complexes that have arrested and backtracked. How TFIIS affects transcription under normal conditions is poorly understood. We identified backtracking sites in human cells using a dominant-negative TFIIS (TFIISDN) that inhibits RNA cleavage and stabilizes backtracked complexes. Backtracking is most frequent within 2 kb of start sites, consistent with slow elongation early in transcription, and in 3' flanking regions where termination is enhanced by TFIISDN, suggesting that backtracked pol II is a favorable substrate for termination. Rescue from backtracking by RNA cleavage also promotes escape from 5' pause sites, prevents premature termination of long transcripts, and enhances activation of stress-inducible genes. TFIISDN slowed elongation rates genome-wide by half, suggesting that rescue of backtracked pol II by TFIIS is a major stimulus of elongation under normal conditions.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: RNA Polimerase II / RNA / Ativação Transcricional / Clivagem do RNA / Elongação da Transcrição Genética / Terminação da Transcrição Genética Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: RNA Polimerase II / RNA / Ativação Transcricional / Clivagem do RNA / Elongação da Transcrição Genética / Terminação da Transcrição Genética Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article