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How and where are nonsense mRNAs degraded in mammalian cells?

Oliver Mühlemann and Jens Lykke-Andersen

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The nonsense-mediated mRNA decay (NMD) pathway is responsible for the rapid degradation of eukaryotic mRNAs on which ribosomes fail to terminate translation properly. NMD thereby contributes to the elimination of aberrant mRNAs, improving the fidelity of gene expression, but also serves to regulate gene expression at the post-transcriptional level. Here we discuss recent evidence as to how and where mRNAs targeted to NMD are degraded in human cells. We discuss accumulating evidence that the decay step of human NMD can be initiated by two different mechanisms: either by SMG6-mediated endonucleolytic cleavage near the aberrant stop codon, or by deadenylation and decapping. While there is evidence that mRNAs targeted for NMD have the capacity to accumulate with other translationally repressed mRNAs in P-bodies, there is currently no evidence that this is required for the degradation of the NMD substrate. It therefore remains an open question whether NMD in human cells is restricted to a particular cellular location or whether it can be initiated wherever translation of the NMD substrate takes place.

Authors

Oliver Mühlemann Corresponding author: oliver.muehlemann@izb.unibe.ch

Jens Lykke-Andersen

This is an open-access article

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If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.