Che-1/AATF binds to RNA polymerase I machinery and sustains ribosomal RNA gene transcription

Cristina Sorino, Valeria Catena, Tiziana Bruno, Francesca De Nicola, Stefano Scalera, Gianluca Bossi, Francesca Fabretti, Miguel Mano, Enrico De Smaele, Maurizio Fanciulli, Simona Iezzi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)5891-5906
Number of pages16
JournalNucleic Acids Research
Volume48
Issue number11
DOIs
Publication statusPublished - Jun 19 2020

ASJC Scopus subject areas

  • Genetics

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