Alu element-containing RNAs maintain nucleolar structure and function

EMBO J. 2015 Nov 12;34(22):2758-74. doi: 10.15252/embj.201591458. Epub 2015 Oct 13.

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.

Keywords: Alu repeat‐containing RNA; RNA‐dependent phase separation; nucleolus structure and function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alu Elements
  • Cell Nucleolus / genetics
  • Cell Nucleolus / metabolism*
  • Genetic Loci*
  • HeLa Cells
  • Humans
  • Nucleic Acid Conformation
  • Oligodeoxyribonucleotides, Antisense / pharmacology
  • 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*

Substances

  • Oligodeoxyribonucleotides, Antisense
  • RNA Precursors
  • RNA, Untranslated
  • RNA Polymerase II