title: Characterization of the Human Transcription Elongation Factor Rtf1: Evidence for Nonoverlapping Functions of Rtf1 and the Paf1 Complex.
abstract: Restores TBP function 1 (Rtf1) is generally considered to be a subunit of the Paf1 complex (PAF1C), a multifunctional protein complex involved in histone modification and transcriptional or posttranscriptional regulation. Rtf1, however, is not stably associated with the PAF1C in most species except Saccharomyces cerevisiae, and its biochemical functions are not well understood. Here, we show that human Rtf1 is a transcription elongation factor that may function independently of the PAF1C. Rtf1 requires "Rtf1 coactivator" activity, which is most likely unrelated to the PAF1C or DSIF, for transcriptional activation in vitro. A mutational study revealed that the Plus3 domain of human Rtf1 is critical for its coactivator-dependent function. Transcriptome sequencing (RNA-seq) and chromatin immunoprecipitation studies in HeLa cells showed that Rtf1 and the PAF1C play distinct roles in regulating the expression of a subset of genes. Moreover, contrary to the finding in S. cerevisiae, the PAF1C was apparently recruited to the genes examined in an Rtf1-independent manner. The present study establishes a role for human Rtf1 as a transcription elongation factor and highlights the similarities and differences between the S. cerevisiae and human Rtf1 proteins.
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
authors.forename: Qing-Fu
authors.initials: QF
authors.lastname: Cao
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Yamamoto
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Isobe
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
authors.forename: Shumpei
authors.initials: S
authors.lastname: Tateno
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Murase
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
authors.forename: Yexi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Nanoparticle Translational Research, Tokyo Medical University, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Handa
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan yyamaguc@bio.titech.ac.jp.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yamaguchi
mesh_terms: D063990:Gene Ontology; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000502:physiology*; D061805:Transcription Elongation, Genetic; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation; D054875:Ubiquitination
chemical_list: D009687:Nuclear Proteins; C501972:PAF1 protein, human; C527330:RTF1 protein, human; D014157:Transcription Factors