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

• Type: Article in International Scientific Journal
• Date: 2008

Authors

Silva, AL (Author) Other; Ribeiro, P (Author) Other; Inacio, A (Author) Other; Liebhaber, SA (Author) Other; Romao, L (Author) Other

Journal

Title: RNA

Vol. 14

Pages: 563-576

ISSN: 1355-8382

Publisher: Cold Spring Harbor Laboratory Press

Indexing

ISI Web of Knowledge - 94 Citations

Scopus - 71 Citations

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14