A nonsense mutation in the fibrillin-1 gene of a Marfan syndrome patient induces NMD and disrupts an exonic splicing enhancer.
A nonsense mutation in the fibrillin-1 (FBN1) gene of a Marfan syndrome (MFS) patient induces in-frame exon skipping of FBN1 exon 51. We present evidence, based on both in vivo and in vitro experiments, that the skipping of this exon is due to the disruption of an SC35-dependent splicing enhancer within exon 51. In addition, this nonsense mutation induces nonsense-mediated decay (NMD), which degrades the normally spliced mRNA in the patient's cells. In contrast to NMD, skipping of FBN1 exon 51 does not require translation.
Caputi
Massimo
M
Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218, USA. maxcaputi@earthlink.net
Kendzior
Raymond J
RJ
Beemon
Karen L
KL
D017398:Alternative Splicing; D001483:Base Sequence; D002478:Cells, Cultured; D003062:Codon; D018389:Codon, Nonsense; D004742:Enhancer Elements, Genetic; D005091:Exons; D000071838:Fibrillin-1; D000071837:Fibrillins; D006801:Humans; D008382:Marfan Syndrome / Q000235:genetics*; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D012322:RNA Precursors; D054392:Adipokines
D003062:Codon; D018389:Codon, Nonsense; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; D012322:RNA Precursors; C000605722:FBN1 protein, human; D054392:Adipokines