Noncoding transcripts in sense and antisense orientation regulate the epigenetic state of ribosomal RNA genes

Cold Spring Harb Symp Quant Biol. 2010:75:357-64. doi: 10.1101/sqb.2010.75.060. Epub 2011 Apr 18.

Abstract

Alternative transcription of the same gene in sense and antisense orientation regulates expression of protein-coding genes. Here we show that noncoding RNA (ncRNA) in sense and antisense orientation also controls transcription of rRNA genes (rDNA). rDNA exists in two types of chromatin--a euchromatic conformation that is permissive to transcription and a heterochromatic conformation that is transcriptionally silent. Silencing of rDNA is mediated by NoRC, a chromatin-remodeling complex that triggers heterochromatin formation. NoRC function requires RNA that is complementary to the rDNA promoter (pRNA). pRNA forms a DNA:RNA triplex with a regulatory element in the rDNA promoter, and this triplex structure is recognized by DNMT3b. The results imply that triplex-mediated targeting of DNMT3b to specific sequences may be a common pathway in epigenetic regulation. We also show that rDNA is transcribed in antisense orientation. The level of antisense RNA (asRNA) is down-regulated in cancer cells and up-regulated in senescent cells. Ectopic asRNA triggers trimethylation of histone H4 at lysine 20 (H4K20me3), suggesting that antisense transcripts guide the histone methyltransferase Suv4-20 to rDNA. The results reveal that noncoding RNAs in sense and antisense orientation are important determinants of the epigenetic state of rDNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Cell Nucleolus / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA, Intergenic / genetics
  • Down-Regulation / genetics
  • Epigenesis, Genetic*
  • Genes, rRNA / genetics*
  • Mice
  • Multiprotein Complexes / metabolism
  • NIH 3T3 Cells
  • Promoter Regions, Genetic / genetics
  • Protein Binding / genetics
  • RNA Stability / genetics
  • RNA, Antisense / genetics
  • RNA, Antisense / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Untranslated / genetics
  • RNA, Untranslated / metabolism*
  • Transcription, Genetic

Substances

  • Baz2a protein, mouse
  • Chromosomal Proteins, Non-Histone
  • DNA, Intergenic
  • Multiprotein Complexes
  • RNA, Antisense
  • RNA, Messenger
  • RNA, Untranslated