Alu element-containing RNAs maintain nucleolar structure and function

• Published in: The EMBO journal 2015-11, Vol.34 (22), p.2758-2774
• Main Authors: Caudron-Herger, Maïwen, Pankert, Teresa, Seiler, Jeanette, Németh, Attila, Voit, Renate, Grummt, Ingrid, Rippe, Karsten
• Format: Article
• Language: English
• Subjects: Alu Elements; Alu repeat-containing RNA; Cell Nucleolus - genetics; Cell Nucleolus - metabolism; Cellular biology; EMBO09; EMBO36; EMBO44; Fluorescence microscopy; Gene loci; Genetic Loci; Genomics; HeLa Cells; Humans; Nucleic Acid Conformation; nucleolus structure and function; Oligodeoxyribonucleotides, Antisense - pharmacology; RNA polymerase; RNA Polymerase II - antagonists & inhibitors; RNA Polymerase II - genetics; RNA Polymerase II - metabolism; RNA Precursors - genetics; RNA Precursors - metabolism; RNA, Untranslated - genetics; RNA, Untranslated - metabolism; RNA-dependent phase separation
• ISSN: 0261-4189; 1460-2075
• DOI: 10.15252/embj.201591458

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 ( alu RNAs) were enriched in the nucleolus. Antisense‐oligo‐mediated depletion of alu RNAs 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 alu RNA sequence increased both nucleolus size and levels of pre‐rRNA, suggesting a functional link between alu RNA, nucleolus integrity and pre‐rRNA synthesis. Furthermore, we show that alu RNAs interact with nucleolin and target ectopic genomic loci to the nucleolus. Our study suggests an alu RNA‐based mechanism that links RNA polymerase I and II activities and modulates nucleolar structure and rRNA production. Synopsis The human genome encodes thousands of Alu repeats of unclear function. This study shows intronic Alu elements transcribed by RNA Pol II to be enriched in the nucleolus where they maintain nucleolar integrity and ensure pre‐rRNA synthesis. Intronic Alu element‐containing RNAs ( alu RNAs) are enriched in the nucleolus. Depletion of alu RNAs disrupts nucleolar structure and impairs rRNA production, while overexpression of alu RNAs increases both nucleolus size and rRNA levels. alu RNAs interact with nucleolin and can target large genomic loci to the nucleolus. alu RNAs are produced by RNA polymerase II and link its activity to rRNA production by RNA polymerase I. Graphical Abstract The human genome encodes thousands of Alu repeats of unclear function. This study shows intronic Alu elements transcribed by RNA Pol II to be enriched in the nucleolus where they maintain nucleolar integrity and ensure pre‐rRNA synthesis.