Abstract

AATF is a central regulator of the cellular outcome upon p53 activation, a finding that has primarily been attributed to its function as a transcription factor. Recent data showed that AATF is essential for ribosome biogenesis and plays a role in rRNA maturation. AATF has been implicated to fulfil this role through direct interaction with rRNA and was identified in several RNA-interactome capture experiments. Here, we provide a first comprehensive analysis of the RNA bound by AATF using CLIP-sequencing. Interestingly, this approach shows predominant binding of the 45S pre-ribosomal RNA precursor molecules. Furthermore, AATF binds to mRNAs encoding for ribosome biogenesis factors as well as snoRNAs. These findings are complemented by an in-depth analysis of the protein interactome of AATF containing a large set of proteins known to play a role in rRNA maturation with an emphasis on the protein-RNA-complexes known to be required for the generation of the small ribosomal subunit (SSU). In line with this finding, the binding sites of AATF within the 45S rRNA precursor localize in close proximity to the SSU cleavage sites. Consequently, our multilayer analysis of the protein-RNA interactome of AATF reveals this protein to be an important hub for protein and RNA interactions involved in ribosome biogenesis.

Details

Title
A protein-RNA interaction atlas of the ribosome biogenesis factor AATF
Author
Kaiser, Rainer W J 1   VIAFID ORCID Logo  ; Ignarski, Michael 1   VIAFID ORCID Logo  ; Van Nostrand, Eric L 2 ; Frese, Christian K 3 ; Jain, Manaswita 4 ; Cukoski, Sadrija 4 ; Heinen, Heide 4 ; Schaechter, Melanie 4 ; Seufert, Lisa 1 ; Bunte, Konstantin 5 ; Frommolt, Peter 6 ; Keller, Patrick 7 ; Helm, Mark 7 ; Bohl, Katrin 1 ; Höhne, Martin 8 ; Schermer, Bernhard 8   VIAFID ORCID Logo  ; Benzing, Thomas 8 ; Höpker, Katja 1 ; Dieterich, Christoph 9 ; Yeo, Gene W 2 ; Roman-Ulrich, Müller 8   VIAFID ORCID Logo  ; Fabretti, Francesca 4 

1  Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany 
2  Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA 
3  Proteomics Core Facility, Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany 
4  Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany 
5  Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany; Bioinformatics Core Facility, Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany 
6  Bioinformatics Core Facility, Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany 
7  Institute of Pharmacy and Biochemistry, Johannes Gutenberg-University Mainz, Mainz, Germany 
8  Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany; Systems Biology of Ageing Cologne, University of Cologne, Cologne, Germany 
9  German Center for Cardiovascular Research (DZHK), Partner site Heidelberg/Mannheim, Heidelberg, Germany; Section of Bioinformatics and Systems Cardiology, Klaus Tschira Institute for Integrative Computational Cardiology and Department of Internal Medicine III, Heidelberg, Germany 
Pages
1-15
Publication year
2019
Publication date
Jul 2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-019-47552-3
ProQuest document ID
2266994748
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.