Proximity of the poly(A)-binding protein to a premature termination codon inhibits mammalian nonsense-mediated mRNA decay

• Tipo: Artigo em Revista Científica Internacional
• Data: 2008

Autores

Silva, AL (Autor) Outra; Ribeiro, P (Autor) Outra; Inacio, A (Autor) Outra; Liebhaber, SA (Autor) Outra; Romao, L (Autor) Outra

Revista

Título: RNA

Vol. 14

Páginas: 563-576

ISSN: 1355-8382

Editora: Cold Spring Harbor Laboratory Press

Indexação

ISI Web of Knowledge - 94 Citações

Scopus - 71 Citações

Outras Informações

ID Authenticus: P-004-1D0

DOI: 10.1261/rna.815108

Abstract (EN): mRNA surveillance pathways selectively clear defective mRNAs from the cell. As such, these pathways serve as important modifiers of genetic disorders. Nonsense-mediated decay (NMD), the most intensively studied surveillance pathway, recognizes mRNAs with premature termination codons (PTCs). In mammalian systems the location of a PTC more than 50 nucleotides 5 ' to the terminal exon-exon junction is a critical determinant of NMD. However, mRNAs with nonsense codons that fulfill this requirement but are located very early in the open reading frame can effectively evade NMD. The unexpected resistance of such mRNAs with AUG-proximal PTCs to accelerated decay suggests that important determinants of NMD remain to be identified. Here, we report that an NMD-sensitive mRNA can be stabilized by artificially tethering the cytoplasmic poly( A) binding protein 1, PABPC1, at a PTC-proximal position. Remarkably, the data further suggest that NMD of an mRNA with an AUG-proximal PTC can also be repressed by PABPC1, which might be brought into proximity with the PTC during cap-dependent translation and 43S scanning. These results reveal a novel parameter of NMD in mammalian cells that can account for the stability of mRNAs with AUG-proximal PTCs. These findings serve to expand current mechanistic models of NMD and mRNA translation.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 14