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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.
Durand, Sébastien; Cougot, Nicolas; Mahuteau-Betzer, Florence; Nguyen, Chi-Hung; Grierson, David S; Bertrand, Edouard; Tazi, Jamal; Lejeune, Fabrice.
Afiliação
  • Durand S; Centre National de la Recherche Scientifique, Institut de Génétique Moléculaire de Montpellier, Université de Montpellier, Montpellier F-34293, France.
J Cell Biol ; 178(7): 1145-60, 2007 Sep 24.
Article em En | MEDLINE | ID: mdl-17893241
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Códon sem Sentido / Estabilidade de RNA / Estruturas Citoplasmáticas / Indóis Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2007 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Códon sem Sentido / Estabilidade de RNA / Estruturas Citoplasmáticas / Indóis Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2007 Tipo de documento: Article