The RNA-binding protein AATF coordinates rRNA maturation

Apoptosis-antagonizing transcription factor (AATF) is a predominantly nuclear protein essential for both embryonic development and tumor growth. Several studies have shown a role of AATF in the modulation of cellular signal transduction pathways such as p53-, mTOR- and HIF-signaling. However, the exact molecular functions underlying its essential nature to cell proliferation and survival have remained elusive. Interestingly, several lines of evidence point towards a pivotal role of this protein in ribosome biogenesis and the maturation of ribosomal RNA. In this study, we identify AATF in a screen for RNA-binding proteins. Importantly, CLIP-sequencing shows a predominant association with 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 characterization of the protein interactome of AATF, again containing a large set of proteins known to play a role in rRNA maturation. Consequently, our multilayer analysis of the protein-RNA interactome of AATF reveals this protein to be a central hub in the coordination of ribosome biogenesis.