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

• Type: Article in International Scientific Journal
• Date: 2012

Authors

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

Journal

Title: Nucleic Acids Research

Vol. 40

Pages: 1160-1173

ISSN: 0305-1048

Publisher: Oxford University Press

Indexing

ISI Web of Knowledge - 40 Citations

Scopus - 21 Citations

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14