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Nonsense-mediated mRNA decay, a simplified view of a complex mechanism

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Nonsense-mediated mRNA decay (NMD) is both a quality controlmechanism and a gene regulation pathway. It has beenstudied for more than 30 years, with an accumulation of manymechanistic details that have often led to debate and hence todifferent models of NMD activation, particularly in higher eukaryotes. Two models seem to be opposed, since the first requiresintervention of the exon junction complex (EJC) to recruitNMD factors downstream of the premature termination codon(PTC), whereas the second involves an EJC-independent mechanismin which NMD factors concentrate in the 3’UTR toinitiate NMD in the presence of a PTC. In this review we describeboth models, giving recent molecular details and providingexperimental arguments supporting one or the othermodel. In the end it is certainly possible to imagine that thesetwo mechanisms co-exist, rather than viewing them as mutuallyexclusive.

Abstract

Nonsense-mediated mRNA decay (NMD) is both a quality controlmechanism and a gene regulation pathway. It has beenstudied for more than 30 years, with an accumulation of manymechanistic details that have often led to debate and hence todifferent models of NMD activation, particularly in higher eukaryotes. Two models seem to be opposed, since the first requiresintervention of the exon junction complex (EJC) to recruitNMD factors downstream of the premature termination codon(PTC), whereas the second involves an EJC-independent mechanismin which NMD factors concentrate in the 3’UTR toinitiate NMD in the presence of a PTC. In this review we describeboth models, giving recent molecular details and providingexperimental arguments supporting one or the othermodel. In the end it is certainly possible to imagine that thesetwo mechanisms co-exist, rather than viewing them as mutuallyexclusive.

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