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Nucleic Acids Res. 2016 Jan 8;44(1):14-23. doi: 10.1093/nar/gkv1218. Epub 2015 Nov 17.

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

Author information

1
Department of biochemistry, Université de Sherbrooke, Sherbrooke, Quebec J1E 4K8, Canada PROTEO, Quebec Network for Research on Protein Function, Structure, and Engineering, Quebec, Canada.
2
Department of biochemistry, Université de Sherbrooke, Sherbrooke, Quebec J1E 4K8, Canada PROTEO, Quebec Network for Research on Protein Function, Structure, and Engineering, Quebec, Canada Inserm U-1192, Laboratoire de Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM), Université de Lille 1, Cité Scientifique, 59655 Villeneuve D'Ascq, France.
3
Department of biochemistry, Université de Sherbrooke, Sherbrooke, Quebec J1E 4K8, Canada PROTEO, Quebec Network for Research on Protein Function, Structure, and Engineering, Quebec, Canada xavier.roucou@usherbrooke.ca.

Abstract

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.

PMID:
26578573
PMCID:
PMC4705651
DOI:
10.1093/nar/gkv1218
[Indexed for MEDLINE]
Free PMC Article

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