Article abstract


Nature Structural & Molecular Biology 15, 842 - 848 (2008)
Published online: 6 July 2008 | doi:10.1038/nsmb.1444

Antisense transcripts are targets for activating small RNAs

Jacob C Schwartz1,2, Scott T Younger1,2, Ngoc-Bich Nguyen1,2, Daniel B Hardy3, Brett P Monia4, David R Corey1,2 & Bethany A Janowski1,2


Agents that activate expression of specific genes to probe cellular pathways or alleviate disease would go beyond existing approaches for controlling gene expression. Duplex RNAs complementary to promoter regions can repress or activate gene expression. The mechanism of these promoter-directed antigene RNAs (agRNAs) has been obscure. Other work has revealed noncoding transcripts that overlap mRNAs. The function of these noncoding transcripts is also not understood. Here we link these two sets of enigmatic results. We find that antisense transcripts are the target for agRNAs that activate or repress expression of progesterone receptor (PR). agRNAs recruit Argonaute proteins to PR antisense transcripts and shift localization of the heterogeneous nuclear ribonucleoprotein-k, RNA polymerase II and heterochromatin protein 1gamma. Our data demonstrate that antisense transcripts have a central role in recognition of the PR promoter by both activating and inhibitory agRNAs.

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  1. Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9041, USA
  2. Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9041, USA.
  3. Department of Obstetrics and Gynaecology, and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 5C1, Canada.
  4. Isis Pharmaceutical, 1896 Rutherford Court, Carlsbad, California 92008, USA.

Correspondence to: David R Corey1,2 e-mail: david.corey@utsouthwestern.edu

Correspondence to: Bethany A Janowski1,2 e-mail: bethany.janowski@utsouthwestern.edu



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