Transcriptional regulation by small RNAs at sequences downstream from 3' gene termini

Nat Chem Biol. 2010 Aug;6(8):621-9. doi: 10.1038/nchembio.400. Epub 2010 Jun 27.


Transcriptome studies reveal many noncoding transcripts overlapping 3' gene termini. The function of these transcripts is unknown. Here we have characterized transcription at the progesterone receptor (PR) locus and identified noncoding transcripts that overlap the 3' end of the gene. Small RNAs complementary to sequences beyond the 3' terminus of PR mRNA modulated expression of PR, recruited argonaute 2 to a 3' noncoding transcript, altered occupancy of RNA polymerase II, induced chromatin changes at the PR promoter and affected responses to physiological stimuli. We found that the promoter and 3' terminal regions of the PR locus are in close proximity, providing a potential mechanism for RNA-mediated control of transcription over long genomic distances. These results extend the potential for small RNAs to regulate transcription to target sequences beyond the 3' termini of mRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics*
  • 3' Untranslated Regions / physiology
  • 5' Untranslated Regions / genetics
  • BRCA1 Protein / biosynthesis
  • BRCA1 Protein / genetics
  • Cell Line
  • Chromatin / metabolism
  • DNA, Complementary / biosynthesis
  • DNA, Complementary / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation / physiology*
  • Gene Targeting
  • Humans
  • Protein Conformation
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Small Cytoplasmic / physiology*


  • 3' Untranslated Regions
  • 5' Untranslated Regions
  • BRCA1 Protein
  • Chromatin
  • DNA, Complementary
  • RNA, Messenger
  • RNA, Small Cytoplasmic