A minor alternative transcript of the fumarylacetoacetate hydrolase gene produces a protein despite being likely subjected to nonsense-mediated mRNA decay

BMC Molecular Biology
Natacha DreumontR M Tanguay

Abstract

Coupling of alternative splicing with nonsense-mediated mRNA decay (NMD) may regulate gene expression. We report here the identification of a nonsense alternative transcript of the fumarylacetoacetate hydrolase (fah) gene, which produces a protein despite the fact that it is subject to NMD. During the characterization of the effects of the W262X nonsense mutation on FAH mRNA metabolism, two alternative transcripts (del100 and del231) of the fah gene were identified. Del100 lacks exon 8 and as a consequence, the reading frame is shifted and a premature termination codon appears at the 3'end of exon 10. Exons 8 and 9 are skipped in del231, without any disruption of the reading frame. Specific amplification of these transcripts demonstrate that they are produced through minor alternative splicing pathways, and that they are not caused by the W262X mutation per se. As shown with an antiserum raised against the C-terminal part of the putative DEL100 protein, the del100 transcript produces a protein, expressed at different levels in various human tissues. Interestingly, the del100 transcript seems to be subjected to nonsense-mediated mRNA decay, as its level was stabilized following a cycloheximide treatment. The del100 and del231 tr...Continue Reading

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Citations

Sep 30, 2016·Journal of Cellular Physiology·María Laura MatosMónica Hebe Vazquez-Levin
Feb 21, 2016·Molecular & Cellular Proteomics : MCP·Jana SieberAndreas E Kulozik
Dec 24, 2013·The Journal of Endocrinology·Michelle C MeloRüdiger W Schulz
May 10, 2005·The Journal of Pharmacology and Experimental Therapeutics·Bela KisDavid W Busija

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Methods Mentioned

BETA
PCR
immunoprecipitation

Software Mentioned

RUST Translation
Proscan

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Alternative splicing

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