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 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.
Ebralidze
Alexander K
AK
Harvard Institutes of Medicine, Harvard Stem Cell Institute, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.
Guibal
Florence C
FC
Steidl
Ulrich
U
Zhang
Pu
P
Lee
Sanghoon
S
Bartholdy
Boris
B
Jorda
Meritxell Alberich
MA
Petkova
Victoria
V
Rosenbauer
Frank
F
Huang
Gang
G
Dayaram
Tajhal
T
Klupp
Johanna
J
O'Brien
Karen B
KB
Will
Britta
B
Hoogenkamp
Maarten
M
Borden
Katherine L B
KL
Bonifer
Constanze
C
Tenen
Daniel G
DG
D000818:Animals; D002460:Cell Line; D018274:Electroporation; D015870:Gene Expression; D006098:Granulocytes / Q000166:cytology / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D018189:Immunomagnetic Separation; D019169:Jurkat Cells; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008957:Models, Genetic; D014176:Protein Biosynthesis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D034622:RNA Interference; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D013601:T-Lymphocytes / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics*; D014158:Transcription, Genetic; D020298:U937 Cells; D000099232:Proto-Oncogene Protein Spi-1
D011518:Proto-Oncogene Proteins; D016372:RNA, Antisense; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1