ArticleMolecular and cellular biology2013
Active stabilization of human endothelial nitric oxide synthase mRNA by hnRNP E1 protects against antisense RNA and microRNAs.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 58 citations in OpenAlex.
- Repurposed hnRNPC binds mature mRNAs and safeguards the mitotic transcriptome.Nucleic acids research · 2026Article
- Hypoxia-Dependent Upregulation of VEGF Relies on β3-Adrenoceptor Signaling in Human Retinal Endothelial and Müller Cells.International journal of molecular sciences · 2025Article
- Endothelial lipid droplets suppress eNOS to link high fat consumption to blood pressure elevation.The Journal of clinical investigation · 2023Article
- Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- The poly(C)-binding protein Pcbp2 is essential for CD4iScience · 2023Article
- Unlocking the potential of RNA-based therapeutics in the lung: current status and future directions.Frontiers in genetics · 2023Review
- 2'-5' oligoadenylate synthetase‑like 1 (OASL1) protects against atherosclerosis by maintaining endothelial nitric oxide synthase mRNA stability.Nature communications · 2022Article
- Drug delivery approaches for HuR-targeted therapy for lung cancer.Advanced drug delivery reviews · 2022Review
- Endothelial Dysfunction Driven by Hypoxia-The Influence of Oxygen Deficiency on NO Bioavailability.Biomolecules · 2021Review
- MicroRNAs and obesity-induced endothelial dysfunction: key paradigms in molecular therapy.Cardiovascular diabetology · 2020Review
- Optimizing cardiac ischemic preconditioning and postconditioning via epitranscriptional regulation.Medical hypotheses · 2020Article
- Review
- Molecular Mechanisms of Nitric Oxide in Cancer Progression, Signal Transduction, and Metabolism.Antioxidants & redox signaling · 2019Review
- Novel Role of Heterogeneous Nuclear Ribonucleoprotein E1 in Regulation of Apoptosis and Autophagy by a Triazole Derivative in Vascular Endothelial Cells.International journal of biological sciences · 2019Article
- hnRNP E1 at the crossroads of translational regulation of epithelial-mesenchymal transition.Journal of cancer metastasis and treatment · 2019Article
- eNOS expression and NO release during hypoxia is inhibited by miR-200b in human endothelial cells.Angiogenesis · 2018Article
- microRNAs regulate nitric oxide release from endothelial cells by targeting NOS3.Journal of thrombosis and thrombolysis · 2018Article
- PCBP1 depletion promotes tumorigenesis through attenuation of p27Journal of experimental & clinical cancer research : CR · 2018Article
- Nitric oxide signalling in cardiovascular health and disease.Nature reviews. Cardiology · 2018Review
- Pulsatile stretch as a novel modulator of amyloid precursor protein processing and associated inflammatory markers in human cerebral endothelial cells.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
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. Importantly, RNA immunoprecipitations and RNA electrophoretic mobility shift assays (EMSAs) revealed the formation of heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1)-containing RNP complexes at these 3'-UTR elements. Knockdown of hnRNP E1 decreased eNOS mRNA half-life, mRNA levels, and protein expression. Significantly, these stabilizing RNP complexes protect eNOS mRNA from the inhibitory effects of its antisense transcript sONE and 3'-UTR-targeting small interfering RNAs (siRNAs), as well as microRNAs, specifically, hsa-miR-765, which targets eNOS mRNA stability determinants. Hypoxia disrupts hnRNP E1/eNOS 3'-UTR interactions via increased Akt-mediated serine phosphorylation (including serine 43) and increased nuclear localization of hnRNP E1. These mechanisms account, at least in part, for the decrease in eNOS mRNA stability under hypoxic conditions. Thus, the stabilization of human eNOS mRNA by hnRNP E1-containing RNP complexes serves as a key protective mechanism against the posttranscriptional inhibitory effects of antisense RNA and microRNAs under basal conditions but is disrupted under hypoxic conditions.
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