Maintenance of an open reading frame as an additional level of scrutiny during splice site selection.
Although nonsense mutations have been associated with the skipping of specific constitutively spliced exons in selected genes, notably the fibrillin gene, the basis for this association is unclear. Now, using chimaeric constructs in a model in vivo expression system, premature termination codons are identified as determinants of splice site selection. Nonsense codon recognition prior to RNA splicing necessitates the ability to read the frame of precursor mRNA in the nucleus. We propose that maintenance of an open reading frame can serve as an additional level of scrutiny during exon definition. This process may have pathogenic and evolutionary significance.
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
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D001483:Base Sequence; D002478:Cells, Cultured; D003062:Codon / Q000235:genetics; D005091:Exons; D000071837:Fibrillins; D005347:Fibroblasts / Q000378:metabolism; D005813:Genes, Synthetic; D015799:Gyrate Atrophy / Q000235:genetics; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000235:genetics*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D009953:Ornithine-Oxo-Acid Transaminase / Q000235:genetics; D016133:Polymerase Chain Reaction; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D013728:Terminator Regions, Genetic
D003062:Codon; D000071837:Fibrillins; D008840:Microfilament Proteins; D012322:RNA Precursors; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D009953:Ornithine-Oxo-Acid Transaminase