Journal
NUCLEIC ACIDS RESEARCH
Volume 43, Issue 13, Pages 6528-6544Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkv588
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Funding
- Fundacao para a Ciencia e a Tecnologia (FCT) [POCI/BIA-BCM/59140/2004, UID/MULTI/04046/2013, SFRH/BD/14273/2003, SFRH/BD/63581/2009]
- Instituto Nacional de Saude Doutor Ricardo Jorge
- Oxford Journals Publisher
- Fundação para a Ciência e a Tecnologia [POCI/BIA-BCM/59140/2004, SFRH/BD/14273/2003, SFRH/BD/63581/2009, 2021.06345.BD] Funding Source: FCT
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Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that recognizes and selectively degrades mRNAs carrying premature termination codons (PTCs). The level of sensitivity of a PTC-containing mRNA to NMD is multifactorial. We have previously shown that human beta-globin mRNAs carrying PTCs in close proximity to the translation initiation AUG codon escape NMD. This was called the 'AUG-proximity effect'. The present analysis of nonsense codons in the human alpha-globin mRNA illustrates that the determinants of the AUG-proximity effect are in fact quite complex, reflecting the ability of the ribosome to re-initiate translation 3' to the PTC and the specific sequence and secondary structure of the translated ORF. These data support a model in which the time taken to translate the short ORF, impacted by distance, sequence, and structure, not only modulates translation re-initiation, but also impacts on the exact boundary of AUG-proximity protection from NMD.
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