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

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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
Creators:
CreatorsEmailORCIDORCID Put Code
Sorino, CristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Catena, ValeriaUNSPECIFIEDorcid.org/0000-0002-9639-1944UNSPECIFIED
Bruno, TizianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Nicola, FrancescaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scalera, StefanoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bossi, GianlucaUNSPECIFIEDorcid.org/0000-0002-2947-1063UNSPECIFIED
Fabretti, FrancescaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mano, MiguelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Smaele, EnricoUNSPECIFIEDorcid.org/0000-0003-4524-4423UNSPECIFIED
Fanciulli, MaurizioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Iezzi, SimonaUNSPECIFIEDorcid.org/0000-0002-7484-5861UNSPECIFIED
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
Uncontrolled Keywords:
KeywordsLanguage
RDNA TRANSCRIPTION; P53 TRANSCRIPTION; BIOGENESIS; UBF; PHOSPHORYLATION; SUBUNIT; GROWTH; IDENTIFICATION; ACTIVATION; EXPRESSIONMultiple languages
Biochemistry & Molecular BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/32949

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