ArticleThe Journal of biological chemistry2014
The A2A adenosine receptor is a dual coding gene: a novel mechanism of gene usage and signal transduction.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Systematic Detection of Alternative Open Reading Frames (altORFs) in Cancer Driver Genes.Journal of molecular evolution · 2026Article
- The organization principles of P. falciparum translation initiation features and their potential as drug targets.Nucleic acids research · 2025Article
- Evaluation of Eukaryotic mRNA Coding Potential.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Readthrough isoform of aquaporin-4 (AQP4) as a therapeutic target for Alzheimer's disease and other proteinopathies.Alzheimer's research & therapy · 2023Review
- The dark proteome: translation from noncanonical open reading frames.Trends in cell biology · 2022Review
- The alternative proteome in neurobiology.Frontiers in cellular neuroscience · 2022Review
- Unraveling the hidden role of a uORF-encoded peptide as a kinase inhibitor of PKCs.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Adenosine AFrontiers in neuroscience · 2021Review
- Pervasive functional translation of noncanonical human open reading frames.Science (New York, N.Y.) · 2020Article
- Novel Players in the Aging Synapse: Impact on Cognition.Journal of caffeine and adenosine research · 2019Review
- A genome-wide association study of bitter and sweet beverage consumption.Human molecular genetics · 2019Article
- Concerted expression of a cell cycle regulator and a metabolic enzyme from a bicistronic transcript in plants.Nature plants · 2019Article
- Recognition of the polycistronic nature of human genes is critical to understanding the genotype-phenotype relationship.Genome research · 2018Review
- Adenosine A2A Receptor Signaling in the Immunopathogenesis of Experimental Autoimmune Encephalomyelitis.Frontiers in immunology · 2018Review
- Article
- Death of a dogma: eukaryotic mRNAs can code for more than one protein.Nucleic acids research · 2016Review
- Immunotherapy in the treatment of non-small cell lung cancer.Lung cancer (Amsterdam, Netherlands) · 2014Review
- Potentiation of B2 receptor signaling by AltB2R, a newly identified alternative protein encoded in the human bradykinin B2 receptor gene.The Journal of biological chemistryArticle
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The A2A adenosine receptor (A2AR) is a G protein-coupled receptor and a major target of caffeine. The A2AR gene encodes alternative transcripts that are initiated from at least two independent promoters. The different transcripts of the A2AR gene contain the same coding region and 3'-untranslated region and different 5'-untranslated regions that are highly conserved among species. We report here that in addition to the production of the A2AR protein, translation from an upstream, out-of-frame AUG of the rat A2AR gene produces a 134-amino acid protein (designated uORF5). An anti-uORF5 antibody recognized a protein of the predicted size of uORF5 in PC12 cells and rat brains. Up-regulation of A2AR transcripts by hypoxia led to increased levels of both the A2AR and uORF5 proteins. Moreover, stimulation of A2AR increased the level of the uORF5 protein via post-transcriptional regulation. Expression of the uORF5 protein suppressed the AP1-mediated transcription promoted by nerve growth factor and modulated the expression of several proteins that were implicated in the MAPK pathway. Taken together, our results show that the rat A2AR gene encodes two distinct proteins (A2AR and uORF5) in an A2AR-dependent manner. Our study reveals a new example of the complexity of the mammalian genome and provides novel insights into the function of A2AR.
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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.