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PMID: 18676813 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Genes & development ·Vol. 22 ·No. 15 ·2008-08-01 ·Pages 2085-92

Ebralidze AK, Guibal FC, Steidl U, Zhang P, Lee S, Bartholdy B, Jorda MA, Petkova V, Rosenbauer F, Huang G, Dayaram T, Klupp J, O'Brien KB, Will B, Hoogenkamp M, Borden KL, Bonifer C, Tenen DG

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.

MeSH Terms
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
Chemicals
Proto-Oncogene Proteins RNA, Antisense RNA, Messenger RNA, Small Interfering Trans-Activators proto-oncogene protein Spi-1
Authors & Affiliations
18 authors, click to expand affiliations / ORCID
Ebralidze Alexander K
Harvard Institutes of Medicine, Harvard Stem Cell Institute, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.
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
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1654808
Published
2008-08-01
Pages
2085-92
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC2492744
Subset
IM
Grants
NCI NIH HHS · R01 CA041456 · United States
NCI NIH HHS · CA41456 · United States
External Links
PubMed source DOI: 10.1101/gad.1654808 PMC Full Text View journal details
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