ArticleRNA (New York, N.Y.)2014
Translation of the human erythropoietin transcript is regulated by an upstream open reading frame in response to hypoxia.
Article in RNA (New York, N.Y.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Erythropoietin levels in patients with sleep apnea: a meta-analysis.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2017Pooled it
- Epigenetic alterations facilitate transcriptional and translational programs in hypoxia.Nature cell biology · 2025Article
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- Translation ofBiomedicines · 2021Article
- Poly(U)-specific endoribonuclease ENDOU promotes translation of human CHOP mRNA by releasing uORF element-mediated inhibition.The EMBO journal · 2021Article
- Combined Short and Long-Read Sequencing Reveals a Complex Transcriptomic Architecture of African Swine Fever Virus.Viruses · 2021Article
- Cancer Plasticity: The Role of mRNA Translation.Trends in cancer · 2021Review
- Mammalian Alternative Translation Initiation Is Mostly Nonadaptive.Molecular biology and evolution · 2020Article
- Small open reading frames and cellular stress responses.Molecular omics · 2019Review
- mRNA-to-protein translation in hypoxia.Molecular cancer · 2019Review
- Impact of FHIT loss on the translation of cancer-associated mRNAs.Molecular cancer · 2017Article
- Long-Read Sequencing of Human Cytomegalovirus Transcriptome Reveals RNA Isoforms Carrying Distinct Coding Potentials.Scientific reports · 2017Article
- Cap-independent translation ensures mTOR expression and function upon protein synthesis inhibition.RNA (New York, N.Y.) · 2017Article
- Ribosome profiling reveals translational regulation of mammalian cells in response to hypoxic stress.BMC genomics · 2017Article
- Comparative transcriptome analysis of Gastrodia elata (Orchidaceae) in response to fungus symbiosis to identify gastrodin biosynthesis-related genes.BMC genomics · 2016Article
- Expression of human Hemojuvelin (HJV) is tightly regulated by two upstream open reading frames in HJV mRNA that respond to iron overload in hepatic cells.Molecular and cellular biology · 2015Article
- Glucose, insulin, and oxygen interplay in placental hypervascularisation in diabetes mellitus.BioMed research international · 2014Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Erythropoietin (EPO) is a key mediator hormone for hypoxic induction of erythropoiesis that also plays important nonhematopoietic functions. It has been shown that EPO gene expression regulation occurs at different levels, including transcription and mRNA stabilization. In this report, we show that expression of EPO is also regulated at the translational level by an upstream open reading frame (uORF) of 14 codons. As judged by comparisons of protein and mRNA levels, the uORF acts as a cis-acting element that represses translation of the main EPO ORF in unstressed HEK293, HepG2, and HeLa cells. However, in response to hypoxia, this repression is significantly released, specifically in HeLa cells, through a mechanism that involves processive scanning of ribosomes from the 5' end of the EPO transcript and enhanced ribosome bypass of the uORF. In addition, we demonstrate that in HeLa cells, hypoxia induces the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) concomitantly with a significant increase of EPO protein synthesis. These findings provide a framework for understanding that production of high levels of EPO induced by hypoxia also involves regulation at the translational level.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.