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Inhibition of nonsense-mediated mRNA decay (NMD) by a new chemical molecule reveals the dynamic of NMD factors in P-bodies: P-body components dynamics

Abstract : In mammals, nonsense-mediated mRNA decay (NMD) is a quality control mechanism that degrades mRNAs harboring a premature termination codon, in order to prevent the synthesis of truncated proteins. To gain insight into NMD mechanism, we identified NMDI 1 (for nonsense-mediated mRNA decay inhibitor 1) as a small molecule inhibitor of the NMD pathway. We characterized the mode of action of this compound and demonstrated that it acts upstream of hUPF1. NMDI 1 induced the loss of interactions between hSMG5 and hUPF1 and the stabilization of hyperphosphorylated isoforms of hUPF1. Incubation of cells with NMDI 1 allowed us to demonstrate that NMD factors and mRNAs subject to NMD transit through processing bodies (P-bodies) as it is the case in yeast. The results suggest a model in which mRNA and NMD factors are sequentially recruited to P-bodies.
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https://www.hal.inserm.fr/inserm-00175728
Contributor : Fabrice Lejeune <>
Submitted on : Monday, October 1, 2007 - 9:34:31 AM
Last modification on : Wednesday, November 4, 2020 - 5:00:05 PM
Long-term archiving on: : Friday, April 9, 2010 - 4:48:08 PM

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Sébastien Durand, Nicolas Cougot, Florence Mahuteau-Betzer, Chi-Hung Nguyen, David Grierson, et al.. Inhibition of nonsense-mediated mRNA decay (NMD) by a new chemical molecule reveals the dynamic of NMD factors in P-bodies: P-body components dynamics. Journal of Cell Biology, Rockefeller University Press, 2007, 178 (7), pp.1145-1160. ⟨10.1083/jcb.200611086⟩. ⟨inserm-00175728⟩

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