Hannig, Katharina and Babl, Virginia and Hergert, Kristin and Maier, Andreas and Pilsl, Michael and Schaechner, Christopher and Stoeckl, Ulrike and Milkereit, Philipp and Tschochner, Herbert and Seufert, Wolfgang and Griesenbeck, Joachim (2019) The C-terminal region of Net1 is an activator of RNA polymerase I transcription with conserved features from yeast to human. PLOS GENETICS, 15 (2): e1008006. ISSN 1553-7404,
Full text not available from this repository. (Request a copy)Abstract
RNA polymerase I (Pol I) synthesizes ribosomal RNA (rRNA) in all eukaryotes, accounting for the major part of transcriptional activity in proliferating cells. Although basal Pol I transcription factors have been characterized in diverse organisms, the molecular basis of the robust rRNA production in vivo remains largely unknown. In S. cerevisiae, the multifunctional Net1 protein was reported to stimulate Pol I transcription. We found that the Pol I-stimulating function can be attributed to the very C-terminal region (CTR) of Net1. The CTR was required for normal cell growth and Pol I recruitment to rRNA genes in vivo and sufficient to promote Pol I transcription in vitro. Similarity with the acidic tail region of mammalian Pol I transcription factor UBF, which could partly functionally substitute for the CTR, suggests conserved roles for CTR-like domains in Pol I transcription from yeast to human. Author summary The production of ribosomes, cellular factories of protein synthesis, is an essential process driving proliferation and cell growth. Ribosome biogenesis is controlled at the level of synthesis of its components, ribosomal proteins and ribosomal RNA. In eukaryotes, RNA polymerase I is dedicated to transcribe the ribosomal RNA. RNA polymerase I has been identified as a potential target for cell proliferation inhibition. Here we describe the C-terminal region of Net1 as an activator of RNA polymerase I transcription in baker's yeast. In the absence of this activator RNA polymerase I transcription is downregulated and cell proliferation is strongly impaired. Strikingly, this activator might be conserved in human cells, which points to a general mechanism. Our discovery will help to gain a better understanding of the molecular basis of ribosomal RNA synthesis and may have implications in developing strategies to control cellular growth.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RIBOSOMAL DNA-TRANSCRIPTION; BLOCK PROTEIN FOB1; BINDING-FACTOR UBF; SACCHAROMYCES-CEREVISIAE; GENE-TRANSCRIPTION; RDNA TRANSCRIPTION; PHOSPHORYLATION SITES; DEPENDENT REGULATION; CHROMATIN STRUCTURES; CDC14 PHOSPHATASE; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie III > Prof. Dr. Herbert Tschochner |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Apr 2020 07:02 |
| Last Modified: | 22 Apr 2020 07:02 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27606 |
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