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https://hdl.handle.net/10316/106517
Title: | Che-1/AATF binds to RNA polymerase I machinery and sustains ribosomal RNA gene transcription | Authors: | Sorino, Cristina Catena, Valeria Bruno, Tiziana De Nicola, Francesca Scalera, Stefano Bossi, Gianluca Fabretti, Francesca Mano, Miguel De Smaele, Enrico Fanciulli, Maurizio Iezzi, Simona |
Issue Date: | 19-Jun-2020 | Publisher: | Oxford University Press | Project: | Italian Association for Cancer Research [15255 to M.F.] Funding for open access charge: Italian Ministery of Health - Ricerca Corrente 2019 |
Serial title, monograph or event: | Nucleic Acids Research | Volume: | 48 | Issue: | 11 | 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. | URI: | https://hdl.handle.net/10316/106517 | ISSN: | 0305-1048 1362-4962 |
DOI: | 10.1093/nar/gkaa344 | Rights: | openAccess |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
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Che-1 AATF binds to RNA polymerase I machinery.pdf | 5.79 MB | Adobe PDF | View/Open |
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