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Title: How far ‘AUG-proximity effect’ goes?
Authors: Pereira, Francisco J.C.
Teixeira, Alexandre
Kong, Jian
Silva, Ana Luísa
Liebhaber, Stephen A.
Romão, Luísa
Keywords: Genómica Funcional e Estrutural
Issue Date: 1-Sep-2012
Publisher: Instituto Nacional de Saúde Doutor Ricardo Jorge, IP
Abstract: Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that recognizes and selectively degrades mRNAs carrying premature termination codons (PTCs). We have previously shown that mRNAs carrying a PTC located in close proximity to the translation initiation AUG codon escape NMD. This was called the “AUG-proximity effect”. The present work illustrates that the extension of the AUG-proximity effect, i.e. to what position in the open reading frame (ORF) an AUG-proximal PTC does not trigger NMD, is different between human a- and b-globin mRNAs. Remarkably, our data also demonstrate that, contrary to what occurs in the b-globin transcripts, a-globin mRNAs carrying an AUG-proximal PTC allow for efficient translation re-initiation, although it only partially explains their NMD resistance. In addition, our results reveal that in the a- and b-globin transcripts, the extension of the AUG-proximity effect is determined by the ORF sequence. Furthermore, we show how the mRNA secondary structure, which is affected by the ORF sequence, determines the AUG-proximity effect extension. Our data point out that the time taken to translate the short ORF, affected by its sequence and stability, besides being involved in modulating translation re-initiation, also plays an important role in establishing the extension of the AUG-proximity effect.
Peer review: yes
Appears in Collections:DGH - Posters/abstracts em congressos internacionais

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