Interaction of PABPC1 with the translation initiation complex is critical to the NMD resistance of AUG-proximal nonsense mutations

• Tipo: Artigo em Revista Científica Internacional
• Data: 2012

Autores

Peixeiro, I (Autor) Outra; Inacio, A (Autor) Outra; Barbosa, C (Autor) Outra; Silva, AL (Autor) Outra; Liebhaber, SA (Autor) Outra; Romao, L (Autor) Outra

Revista

Título: Nucleic Acids Research

Vol. 40

Páginas: 1160-1173

ISSN: 0305-1048

Editora: Oxford University Press

Indexação

ISI Web of Knowledge - 40 Citações

Scopus - 21 Citações

Outras Informações

ID Authenticus: P-002-DCV

DOI: 10.1093/nar/gkr820

Abstract (EN): Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that recognizes and rapidly degrades mRNAs containing premature termination codons (PTC). The strength of the NMD response appears to reflect multiple determinants on a target mRNA. We have previously reported that mRNAs containing PTCs in close proximity to the translation initiation codon (AUG-proximal PTCs) can substantially evade NMD. Here, we explore the mechanistic basis for this NMD resistance. We demonstrate that translation termination at an AUG-proximal PTC lacks the ribosome stalling that is evident in an NMD-sensitive PTC. This difference is associated with demonstrated interactions of the cytoplasmic poly(A)-binding protein 1, PABPC1, with the cap-binding complex subunit, eIF4G and the 40S recruitment factor eIF3 as well as the ribosome release factor, eRF3. These interactions, in combination, underlie critical 3'-5' linkage of translation initiation with efficient termination at the AUG-proximal PTC and contribute to an NMD-resistant PTC definition at an early phase of translation elongation.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 14