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

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 a...

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Bibliographic Details
Published in:Genes & development Vol. 22; no. 15; p. 2085
Main Authors: Ebralidze, Alexander K, Guibal, Florence C, Steidl, Ulrich, Zhang, Pu, Lee, Sanghoon, Bartholdy, Boris, Jorda, Meritxell Alberich, Petkova, Victoria, Rosenbauer, Frank, Huang, Gang, Dayaram, Tajhal, Klupp, Johanna, O'Brien, Karen B, Will, Britta, Hoogenkamp, Maarten, Borden, Katherine L B, Bonifer, Constanze, Tenen, Daniel G
Format: Journal Article
Language:English
Published: United States 01.08.2008
Subjects:
Animals
Cell Line
Electroporation
Gene Expression
Granulocytes - cytology
Granulocytes - metabolism
HL-60 Cells
Humans
Immunomagnetic Separation
Jurkat Cells
Macrophages - metabolism
Mice
Models, Genetic
Protein Biosynthesis
Proto-Oncogene Proteins - genetics
Regulatory Sequences, Nucleic Acid - genetics
RNA Interference
RNA, Antisense - genetics
RNA, Antisense - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
RNA, Small Interfering - metabolism
T-Lymphocytes - metabolism
Trans-Activators - genetics
Transcription, Genetic
U937 Cells
ISSN:0890-9369
Online Access:Get more information
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Summary: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.
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ISSN:0890-9369
DOI:10.1101/gad.1654808