The A2A Adenosine Receptor Is a Dual Coding Gene

Lee, Chien Fei; Lai, Hsin Lin; Lee, Yi Chao; Chien, Chen Li; Chern, Yijuang

doi:10.1074/jbc.m113.509059

Cited by 29 publications

(13 citation statements)

References 62 publications

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“…A 2A R activation stimulates the cyclic AMP-protein kinase A (PKA) pathway by coupling to Gs protein in peripheral tissues and NF-κB is a PKA downstream gene target [36][37][38]. We observed that A 2A R activation could inhibit the nuclear translocation of NF-κB by decreasing phosphorylation of IκBα via PKA in macrophages.…”

Section: Discussionmentioning

confidence: 90%

The mutual regulation between miR-214 and A2AR signaling plays an important role in inflammatory response

Zhao

Liu

Yang

et al. 2015

Cellular Signalling

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Section: Discussionmentioning

confidence: 90%

The mutual regulation between miR-214 and A2AR signaling plays an important role in inflammatory response

Zhao

Liu

Yang

et al. 2015

Cellular Signalling

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“…There is accumulating evidence of functional ORFs CDS in mammalian mRNAs, and computational approaches predict a large number of ORFs CDS in human and murine cDNAs and transcripts. Several cDNAs containing the annotated CDS and an ORFs CDS ligated into expression vectors generate a small protein in addition to the larger annotated proteins in cultured cells and in vivo . These remarkable observations confirm a counterintuitive feature of mammalian ribosomes which are able to decode ORFs CDS in addition to annotated CDSs in the same transcripts.…”

Section: Translation Outside Of Annotated Cdss: Delinquent Translatiomentioning

confidence: 99%

Small Proteins Encoded by Unannotated ORFs are Rising Stars of the Proteome, Confirming Shortcomings in Genome Annotations and Current Vision of an mRNA

et al. 2017

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Short ORF-encoded peptides and small proteins in eukaryotes have been hiding in the shadow of large proteins for a long time. Recently, improved identifications in MS-based proteomics and ribosome profiling resulted in the detection of large numbers of small proteins. The variety of functions of small proteins is also emerging. It seems to be the right time to reflect on why small proteins remained invisible. In addition to the obvious technical challenge of detecting small proteins, they were mostly forgotten from annotations and they escaped detection because they were not sought. In this review, we identify conventions that need to be revisited, including the assumption that mature mRNAs carry only one coding sequence. The large-scale discovery of small proteins and of their functions will require changing some paradigms and undertaking the annotation of ORFs that are still largely perceived as irrelevant coding information compared to already annotated coding sequences.

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“…Over the past two decades, several refCDS/altORF doublets have been discovered in mammals. These include INK4a/ARF ( 55 ), histone H4/OGP ( 65 ), XLalphas/ALEX ( 45 , 66 ), RPP14/HsHTD2 ( 46 ), PrP/altPrP ( 67 ), ATXN1/altATXN1 ( 68 ), A 2A R/uORF5 ( 69 ), MKKS/uMKKS1 and uMKKS2 ( 70 ) and AT 1a R/PEP7 ( 71 ). Remarkably and perhaps not coincidentatly, some alternative proteins functionally interact with their respective reference proteins.…”

Section: Experimental Evidence For the Translation Of Altormentioning

confidence: 99%

“…ATXN1/altATXN1 co-localize in nuclear foci and directly interact ( 68 ). The stimulation of A 2A R by adenosine increases the expression of uORF5 through the activation of protein kinase A ( 69 ). PEP7 blocks the beta-arrestin dependent signaling pathway of AT 1a R ( 71 ).…”

Section: Experimental Evidence For the Translation Of Altormentioning

confidence: 99%

Death of a dogma: eukaryotic mRNAs can code for more than one protein

2015

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mRNAs carry the genetic information that is translated by ribosomes. The traditional view of a mature eukaryotic mRNA is a molecule with three main regions, the 5′ UTR, the protein coding open reading frame (ORF) or coding sequence (CDS), and the 3′ UTR. This concept assumes that ribosomes translate one ORF only, generally the longest one, and produce one protein. As a result, in the early days of genomics and bioinformatics, one CDS was associated with each protein-coding gene. This fundamental concept of a single CDS is being challenged by increasing experimental evidence indicating that annotated proteins are not the only proteins translated from mRNAs. In particular, mass spectrometry (MS)-based proteomics and ribosome profiling have detected productive translation of alternative open reading frames. In several cases, the alternative and annotated proteins interact. Thus, the expression of two or more proteins translated from the same mRNA may offer a mechanism to ensure the co-expression of proteins which have functional interactions. Translational mechanisms already described in eukaryotic cells indicate that the cellular machinery is able to translate different CDSs from a single viral or cellular mRNA. In addition to summarizing data showing that the protein coding potential of eukaryotic mRNAs has been underestimated, this review aims to challenge the single translated CDS dogma.

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The A2A Adenosine Receptor Is a Dual Coding Gene

Cited by 29 publications

References 62 publications

The mutual regulation between miR-214 and A2AR signaling plays an important role in inflammatory response

The mutual regulation between miR-214 and A2AR signaling plays an important role in inflammatory response

Small Proteins Encoded by Unannotated ORFs are Rising Stars of the Proteome, Confirming Shortcomings in Genome Annotations and Current Vision of an mRNA

Death of a dogma: eukaryotic mRNAs can code for more than one protein

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