Transcriptional silencing by hairpin RNAs complementary to a gene promoter

Yongjun Chu, Roya Kalantari, David W. Dodd, David R. Corey

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Double-stranded RNAs can target gene promoters and inhibit transcription. To date, most research has focused on synthetic RNA duplexes. Transcriptional silencing by hairpin RNAs would facilitate a better understanding of endogenous RNA-mediated regulation of transcription within cells. Here we examine transcriptional silencing of progesterone receptor (PR) expression by hairpin RNAs. We identify the guide strand as the strand complementary to an antisense transcript at the PR promoter and that hairpin RNAs are active transcriptional silencing agents. The sequence of the hairpin loop affects activity, with the highest activity achieved when the loop has the potential for full complementarity to the antisense transcript target. Introduction of centrally mismatched bases relative to the target transcript does not prevent transcriptional silencing unless the mismatches are present on both the guide and passenger strands. These data demonstrate that hairpin RNAs can cause transcriptional silencing and offer insights into the mechanism of gene modulation by RNAs that target gene promoters.

Original languageEnglish (US)
Pages (from-to)147-151
Number of pages5
JournalNucleic Acid Therapeutics
Volume22
Issue number3
DOIs
StatePublished - Jun 1 2012

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Drug Discovery

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