title: Alu element-containing RNAs maintain nucleolar structure and function.
abstract: Non-coding RNAs play a key role in organizing the nucleus into functional subcompartments. By combining fluorescence microscopy and RNA deep-sequencing-based analysis, we found that RNA polymerase II transcripts originating from intronic Alu elements (aluRNAs) were enriched in the nucleolus. Antisense-oligo-mediated depletion of aluRNAs or drug-induced inhibition of RNA polymerase II activity disrupted nucleolar structure and impaired RNA polymerase I-dependent transcription of rRNA genes. In contrast, overexpression of a prototypic aluRNA sequence increased both nucleolus size and levels of pre-rRNA, suggesting a functional link between aluRNA, nucleolus integrity and pre-rRNA synthesis. Furthermore, we show that aluRNAs interact with nucleolin and target ectopic genomic loci to the nucleolus. Our study suggests an aluRNA-based mechanism that links RNA polymerase I and II activities and modulates nucleolar structure and rRNA production.
authors.affiliation: Genome Organization & Function, German Cancer Research Center (DKFZ) Bioquant Center, Heidelberg, Germany m.caudron@dkfz.de karsten.rippe@dkfz.de.
authors.forename: Maïwen
authors.initials: M
authors.lastname: Caudron-Herger
authors.affiliation: Genome Organization & Function, German Cancer Research Center (DKFZ) Bioquant Center, Heidelberg, Germany.
authors.forename: Teresa
authors.initials: T
authors.lastname: Pankert
authors.affiliation: Molecular Biology of the Cell II, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Seiler
authors.affiliation: Department of Biochemistry III, Biochemistry Center Regensburg University of Regensburg, Regensburg, Germany.
authors.forename: Attila
authors.initials: A
authors.lastname: Németh
authors.affiliation: Molecular Biology of the Cell II, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Renate
authors.initials: R
authors.lastname: Voit
authors.affiliation: Molecular Biology of the Cell II, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Grummt
authors.affiliation: Genome Organization & Function, German Cancer Research Center (DKFZ) Bioquant Center, Heidelberg, Germany m.caudron@dkfz.de karsten.rippe@dkfz.de.
authors.forename: Karsten
authors.initials: K
authors.lastname: Rippe
mesh_terms: D020087:Alu Elements; D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism*; D056426:Genetic Loci; D006367:HeLa Cells; D006801:Humans; D009690:Nucleic Acid Conformation; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D012319:RNA Polymerase II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism*; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*
chemical_list: D020319:Oligodeoxyribonucleotides, Antisense; D012322:RNA Precursors; D022661:RNA, Untranslated; D012319:RNA Polymerase II
keywords: Alu repeat‐containing RNA; RNA‐dependent phase separation; nucleolus structure and function