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Identification of an Alternative Exon in a GABA Receptor Gene

Abstract

The central dogma of biology states that DNA is transcribed into mRNA, which is then translated into proteins. In order for translation to occur, pre-mRNAs first must be processed. In pre-mRNA processing, parts of the nucleotide sequence called introns are spliced out from the transcript, so the final mRNA is made up entirely of exons. In alternative splicing, an exon is spliced out of the pre-mRNA transcript much like an intron. An mRNA transcript produced as a result of alternative splicing could produce a different protein than the mRNA without alternative splicing. Alternative splicing of an mRNA transcript could also result in a premature termination codon (PTC) within the mRNA sequence. This premature termination codon causes translation to stop before the full transcript has been translated, resulting in a truncated protein. Nonsense Mediated Decay (NMD) functions by degrading mRNA transcripts containing a PTC. NMD occurs during translation by an intricate series of protein-protein and protein-mRNA interactions that detect a PTC and result in the cleavage of PTC-containing mRNAs. We discovered an alternative exon in a zebrafish GABA receptor gene that leads to a PTC when excluded from the final mRNA and investigated the role of NMD in degrading the PTC-containing transcript

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