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

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.

• Authors: 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
• Journal: Genes & development (Genes Dev) Vol. 22 Issue 15 Pg. 2085-92 (Aug 01 2008) ISSN: 0890-9369 [Print] United States
• PMID: 18676813 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Proto-Oncogene Proteins
• RNA, Antisense
• RNA, Messenger
• RNA, Small Interfering
• Trans-Activators
• proto-oncogene protein Spi-1

Topics

• Animals
• Cell Line
• Electroporation
• Gene Expression
• Granulocytes (cytology, metabolism)
• HL-60 Cells
• Humans
• Immunomagnetic Separation
• Jurkat Cells
• Macrophages (metabolism)
• Mice
• Models, Genetic
• Protein Biosynthesis
• Proto-Oncogene Proteins (genetics)
• RNA Interference
• RNA, Antisense (genetics, metabolism)
• RNA, Messenger (genetics, metabolism)
• RNA, Small Interfering (metabolism)
• Regulatory Sequences, Nucleic Acid (genetics)
• T-Lymphocytes (metabolism)
• Trans-Activators (genetics)
• Transcription, Genetic
• U937 Cells