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A noncoding RNA regulates human protease-activated receptor-1 gene during embryogenesis
Nageswara R Madamanchi1, Zhao Y Hu, Fengzhi Li
1Carolina Cardiovascular Biology Center, Department of Medicine, University of North Carolina, Chapel Hill, NC 27599-7126, USA.
Biochimica Et Biophysica Acta
|June 27, 2002
Summary
A novel noncoding RNA (ncR-uPAR) regulates human protease-activated receptor-1 (PAR-1) gene expression. This RNA is crucial for PAR-1 function during embryonic vascular development.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- Protease-activated receptor-1 (PAR-1) activation by thrombin is vital for vascular integrity.
- PAR-1 is implicated in atherosclerosis, angiogenesis, and tumor metastasis.
- Understanding PAR-1 gene regulation is critical for these processes.
Purpose of the Study:
- To investigate the regulatory elements of the human PAR-1 promoter.
- To identify novel factors influencing PAR-1 gene expression during development.
Main Methods:
- In vitro analysis of the PAR-1 promoter using luciferase assays.
- Generation and analysis of transgenic mice with PAR-1 5' flanking sequences driving a LacZ reporter.
- Identification and characterization of a novel noncoding RNA (ncR-uPAR).
Main Results:
- A positive regulatory element for PAR-1 was located between -4.2 and -3.2 kb.
- Transgenic PAR-1 expression in vivo was observed only with the 4.1 kb construct during embryonic development, specifically in arteries.
- A novel noncoding RNA, ncR-uPAR, was identified upstream of PAR-1 and found to upregulate PAR-1 promoter activity and mRNA expression in vitro.
Conclusions:
- A novel noncoding RNA (ncR-uPAR) plays a role in regulating human PAR-1 gene expression.
- ncR-uPAR appears to act in trans on the adjacent PAR-1 promoter.
- This noncoding RNA is important for PAR-1 gene expression during embryonic growth and vascular development.