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

被引:145
作者
Ebralidze, Alexander K. [1 ]
Guibal, Florence C. [1 ]
Steidl, Ulrich [2 ,3 ]
Zhang, Pu [1 ]
Lee, Sanghoon [1 ]
Bartholdy, Boris [1 ]
Jorda, Meritxell Alberich [1 ]
Petkova, Victoria [1 ]
Rosenbauer, Frank [4 ]
Huang, Gang [1 ]
Dayaram, Tajhal [1 ]
Klupp, Johanna [1 ]
O'Brien, Karen B. [1 ]
Will, Britta [1 ]
Hoogenkamp, Maarten [5 ]
Borden, Katherine L. B. [6 ,7 ]
Bonifer, Constanze [5 ]
Tenen, Daniel G. [1 ]
机构
[1] Harvard Univ, Sch Med, Harbin Inst Med, Harvard Stem Cell Inst, Boston, MA 02115 USA
[2] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA
[3] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Bronx, NY 10461 USA
[4] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany
[5] Univ Leeds, St Jamess Univ Hosp, Leeds Inst Mol Med, Leeds LS7 4JS, W Yorkshire, England
[6] Univ Montreal, Dept Pathol & Cell Biol, Montreal, PQ H3T 1J4, Canada
[7] Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3T 1J4, Canada
关键词
noncoding antisense RNA; upstream and intronic regulatory elements; coordinated expression of the target and regulator; translation stalling;
D O I
10.1101/gad.1654808
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:2085 / 2092
页数:8
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