A noncoding RNA regulates human protease-activated receptor-1 gene during embryogenesis.
Activation of the human protease-activated receptor-1 (PAR-1) by thrombin leads to myriad functions essential for maintaining vascular integrity. Upregulation of PAR-1 expression is considered important in atherosclerosis, angiogenesis and tumor metastasis. In vitro analysis of the human PAR-1 promoter function revealed a positive regulatory element between -4.2 and -3.2 kb of the transcription start site. This element was examined in transgenic mice containing either 4.1 or 2.9 kb of the 5' flanking sequence driving a LacZ reporter gene. Only the 4.1 kb PAR-1 transgene was expressed in vivo and only during embryonic development. The transgene expression was observed only in developing arteries and not in veins. Further examination of this putative regulatory sequence identified a novel noncoding RNA (ncR-uPAR:noncoding RNA upstream of the PAR-1) gene at -3.4 kb. The ncR-uPAR upregulated PAR-1-core promoter-driven luciferase activity and mRNA expression in vitro in a Pol II-dependent manner. This noncoding RNA appears to act in trans, albeit locally at the adjacent PAR-1 promoter. These data suggest that an untranslated RNA plays a role in PAR-1 gene expression during embryonic growth.
Madamanchi
Nageswara R
NR
Carolina Cardiovascular Biology Center, Department of Medicine, University of North Carolina, Chapel Hill, NC 27599-7126, USA.
Hu
Zhao Y
ZY
Li
Fengzhi
F
Horaist
Chris
C
Moon
Sung-Kwon
SK
Patterson
Cam
C
Runge
Marschall S
MS
Ruef
Johannes
J
Fritz
Pamela H
PH
Aaron
Joann
J
D000818:Animals; D001158:Arteries / Q000166:cytology / Q000196:embryology; D001483:Base Sequence; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D022661:RNA, Untranslated; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin; D011993:Recombinant Fusion Proteins