Premature termination codon readthrough in human cells occurs in novel cytoplasmic foci and requires UPF proteins.

J Cell Sci 2017 Sep 25;130(18):3009-3022. Epub 2017 Jul 25.

Univ. Lille, UMR8161 - M3T - Mechanisms of Tumorigenesis and Target Therapies, 59000 Lille, France

Nonsense-mutation-containing messenger ribonucleoprotein particles (mRNPs) transit through cytoplasmic foci called P-bodies before undergoing nonsense-mediated mRNA decay (NMD), a cytoplasmic mRNA surveillance mechanism. This study shows that the cytoskeleton modulates transport of nonsense-mutation-containing mRNPs to and from P-bodies. Impairing the integrity of cytoskeleton causes inhibition of NMD. The cytoskeleton thus plays a crucial role in NMD. Interestingly, disruption of actin filaments results in both inhibition of NMD and activation of premature termination codon (PTC) readthrough, while disruption of microtubules causes only NMD inhibition. Activation of PTC readthrough occurs concomitantly with the appearance of cytoplasmic foci containing UPF proteins and mRNAs with nonsense mutations but lacking the P-body marker DCP1a. These findings demonstrate that in human cells, PTC readthrough occurs in novel 'readthrough bodies' and requires the presence of UPF proteins.

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http://dx.doi.org/10.1242/jcs.198176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5612172PMC
September 2017
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