Inhibition of nonsense-mediated mRNA decay (NMD) by a new chemical molecule reveals the dynamic of NMD factors in P-bodies - Inserm - Institut national de la santé et de la recherche médicale 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 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.
Fichier principal
Vignette du fichier
Manuscript_Durand_HAL.pdf (3.09 Mo) Télécharger le fichier
Suppl_Data_Durand_HAL.pdf (495.5 Ko) Télécharger le fichier
Format : Autre

Dates et versions

inserm-00175728 , version 1 (01-10-2007)

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: P-body components dynamics. Journal of Cell Biology, 2007, 178 (7), pp.1145-1160. ⟨10.1083/jcb.200611086⟩. ⟨inserm-00175728⟩
360 Consultations
938 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More