Sorino, Cristina, Catena, Valeria ORCID: 0000-0002-9639-1944, Bruno, Tiziana, De Nicola, Francesca, Scalera, Stefano, Bossi, Gianluca ORCID: 0000-0002-2947-1063, Fabretti, Francesca, Mano, Miguel, De Smaele, Enrico ORCID: 0000-0003-4524-4423, Fanciulli, Maurizio and Iezzi, Simona ORCID: 0000-0002-7484-5861 (2020). Che-1/AATF binds to RNA polymerase I machinery and sustains ribosomal RNA gene transcription. Nucleic Acids Res., 48 (11). S. 5891 - 5907. OXFORD: OXFORD UNIV PRESS. ISSN 1362-4962
Full text not available from this repository.Abstract
Originally identified as an RNA polymerase II interactor, Che-1/AATF (Che-1) has now been recognized as a multifunctional protein involved in cell-cycle regulation and cancer progression, as well as apoptosis inhibition and response to stress. This protein displays a peculiar nucleolar localization and it has recently been implicated in pre-rRNA processing and ribosome biogenesis. Here, we report the identification of a novel function of Che-1 in the regulation of ribosomal RNA (rRNA) synthesis, in both cancer and normal cells. We demonstrate that Che-1 interacts with RNA polymerase I and nucleolar upstream binding factor (UBF) and promotes RNA polymerase I-dependent transcription. Furthermore, this protein binds to the rRNA gene (rDNA) promoter and modulates its epigenetic state by contrasting the recruitment of HDAC1. Che-1 downregulation affects RNA polymerase I and UBF recruitment on rDNA and leads to reducing rDNA promoter activity and 47S pre-rRNA production. Interestingly, Che-1 depletion induces abnormal nucleolar morphology associated with re-distribution of nucleolar proteins. Finally, we show that upon DNA damage Che-1 re-localizes from rDNA to TP53 gene promoter to induce cell-cycle arrest. This previously uncharacterized function of Che-1 confirms the important role of this protein in the regulation of ribosome biogenesis, cellular proliferation and response to stress.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||||||||||
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URN: | urn:nbn:de:hbz:38-329499 | ||||||||||||||||||||||||||||||||||||||||||||||||
DOI: | 10.1093/nar/gkaa344 | ||||||||||||||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | Nucleic Acids Res. | ||||||||||||||||||||||||||||||||||||||||||||||||
Volume: | 48 | ||||||||||||||||||||||||||||||||||||||||||||||||
Number: | 11 | ||||||||||||||||||||||||||||||||||||||||||||||||
Page Range: | S. 5891 - 5907 | ||||||||||||||||||||||||||||||||||||||||||||||||
Date: | 2020 | ||||||||||||||||||||||||||||||||||||||||||||||||
Publisher: | OXFORD UNIV PRESS | ||||||||||||||||||||||||||||||||||||||||||||||||
Place of Publication: | OXFORD | ||||||||||||||||||||||||||||||||||||||||||||||||
ISSN: | 1362-4962 | ||||||||||||||||||||||||||||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||||||||||||||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||
Subjects: | no entry | ||||||||||||||||||||||||||||||||||||||||||||||||
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URI: | http://kups.ub.uni-koeln.de/id/eprint/32949 |
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