LAUSR

ABSTRACT 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. Summary: The cytoskeleton transports premature termination codon-containing mRNAs to be degraded by nonsense-mediated decay or to be read through in specific cytoplasmic foci called readthrough bodies.