PU.1 expression is modulated by the balance of functional sense and antisense RNAs regulated by a shared cis-regulatory element

Alexander K. Ebralidze, Florence C. Guibal, Ulrich Steidl, Pu Zhang, Sanghoon Lee, Boris Bartholdy, Meritxell Alberich Jorda, Victoria Petkova, Frank Rosenbauer, Gang Huang, Tajhal Dayaram, Johanna Klupp, Karen B. O'Brien, Britta Will, Maarten Hoogenkamp, Katherine L.B. Borden, Constanze Bonifer, Daniel G. Tenen

Research output: Contribution to journalArticlepeer-review

149 Scopus citations

Abstract

The transcription factor PU.1 is an important regulator of hematopoiesis; precise expression levels are critical for normal hematopoietic development and suppression of leukemia. We show here that noncoding antisense RNAs are important modulators of proper dosages of PU.1. Antisense and sense RNAs are regulated by shared evolutionarily conserved cis-regulatory elements, and we can show that antisense RNAs inhibit PU.1 expression by modulating mRNA translation. We propose that such antisense RNAs will likely be important in the regulation of many genes and may be the reason for the large number of overlapping complementary transcripts with so far unknown function.

Original languageEnglish (US)
Pages (from-to)2085-2092
Number of pages8
JournalGenes and Development
Volume22
Issue number15
DOIs
StatePublished - Aug 1 2008

Keywords

  • Coordinated expression of the target and regulator
  • Noncoding antisense RNA
  • Translation stalling
  • Upstream and intronic regulatory elements

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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