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RESEARCH PRODUCT
A protein-RNA interaction atlas of the ribosome biogenesis factor AATF
Thomas BenzingKatja HöpkerRoman-ulrich MüllerMichael IgnarskiChristoph DieterichChristoph DieterichLisa SeufertBernhard SchermerMartin HöhneMelanie SchaechterKatrin BohlFrancesca FabrettiSadrija CukoskiHeide HeinenRainer W.j. KaiserManaswita JainEric L. Van NostrandChristian K. FreseKonstantin BuntePeter FrommoltPatrick KellerGene W. YeoMark Helmsubject
0301 basic medicineRibosomal ProteinsRegulatorRibosome biogenesisProteomic analysislcsh:MedicineInteractomeArticleCell Line03 medical and health sciencesMice0302 clinical medicineRNA PrecursorsAnimalsHumansSmall nucleolar RNABinding sitelcsh:ScienceTranscription factor030304 developmental biologyRNA metabolism0303 health sciencesMultidisciplinaryBinding SitesChemistrylcsh:RRNARibosomal RNACell biologyRibosome Subunits SmallRepressor Proteins030104 developmental biologyHEK293 Cells030220 oncology & carcinogenesisRNAlcsh:QApoptosis Regulatory ProteinsRibosomes030217 neurology & neurosurgeryProtein Bindingdescription
AbstractAATF 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.
year | journal | country | edition | language |
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2018-10-17 | Scientific Reports |