Inhibition of nonsense-mediated mRNA decay (NMD) by a new chemical molecule reveals the dynamic of NMD factors in P-bodies. - Institut Curie Accéder directement au contenu
Article Dans Une Revue Journal of Cell Biology Année : 2007

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

Résumé

In mammals, nonsense-mediated mRNA decay (NMD) is a quality-control mechanism that degrades mRNA harboring a premature termination codon to prevent the synthesis of truncated proteins. To gain insight into the NMD mechanism, we identified NMD inhibitor 1 (NMDI 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 is the case in yeast. The results suggest a model in which mRNA and NMD factors are sequentially recruited to P-bodies.

Domaines

Chimie organique

Dates et versions

hal-00259111 , version 1 (26-02-2008)

Identifiants

Citer

Sébastien Durand, Nicolas Cougot, Florence Mahuteau-Betzer, Chi-Hung Nguyen, David S. Grierson, et al.. Inhibition of nonsense-mediated mRNA decay (NMD) by a new chemical molecule reveals the dynamic of NMD factors in P-bodies.. Journal of Cell Biology, 2007, 178 (7), pp.1145-60. ⟨10.1083/jcb.200611086⟩. ⟨hal-00259111⟩
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