Active stabilization of human endothelial nitric oxide synthase mRNA by hnRNP E1 protects against antisense RNA and microRNAs.

Human endothelial nitric oxide synthase (eNOS) mRNA is highly stable in endothelial cells (ECs). Posttranscriptional regulation of eNOS mRNA stability is an important component of eNOS regulation, especially under hypoxic conditions. Here, we show that the human eNOS 3' untranslated region (3' UTR) contains multiple, evolutionarily conserved pyrimidine (C and CU)-rich sequence elements that are both necessary and sufficient for mRNA stabilization.

The expression of endothelial nitric-oxide synthase is controlled by a cell-specific histone code.

Expression of endothelial nitric-oxide synthase (eNOS) mRNA is highly restricted to the endothelial cell layer of medium to large sized arterial blood vessels. Here we assessed the chromatin environment of the eNOS gene in expressing and nonexpressing cell types. Within endothelial cells, but not a variety of nonendothelial cells, the nucleosomes that encompassed the eNOS core promoter and proximal downstream coding regions were highly enriched in acetylated histones H3 and H4 and methylated lysine 4 of histone H3.

Post-transcriptional regulation of endothelial nitric-oxide synthase by an overlapping antisense mRNA transcript.

Endothelial nitric-oxide synthase (eNOS) mRNA levels are abnormal in diseases of the cardiovascular system, but changes in gene expression cannot be accounted for by transcription alone. We found evidence for the existence of an antisense mRNA (sONE) that is derived from a transcription unit (NOS3AS) on the opposite DNA strand from which the human eNOS (NOS3) mRNA is transcribed at human chromosome 7q36. The genes are oriented in a tail-to-tail configuration, and the mRNAs encoding sONE and eNOS are complementary for 662 nucleotides.

Role of the 3'-untranslated region of human endothelin-1 in vascular endothelial cells. Contribution to transcript lability and the cellular heat shock response.

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide expressed in the vascular endothelium. Stringent control over ET-1 expression is achieved through a highly regulated promoter and rapid mRNA turnover. Since little is known about mechanisms governing ET-1 post-transcriptional regulation, and changes in ET-1 mRNA stability are implicated in disease processes, we characterized these pathways using a variety of functional approaches.

Endothelial nitric oxide synthase: a new paradigm for gene regulation in the injured blood vessel.

Advances in our understanding of the molecular mechanisms involved in the constitutive and regulated expression of endothelial nitric oxide synthase (eNOS) mRNA expression present a new level of complexity to the study of endothelial gene regulation in health and disease. Recent studies highlight the contribution of both transcription and RNA stability to net steady-state mRNA levels of eNOS in vascular endothelium, introducing a new paradigm to gene regulation in the injured blood vessel. Constitutive eNOS expression is dependent on basal transcription machinery in the core promoter, involving positive and negative protein-protein and protein-DNA interactions.