Mutations in the NDUFS4 gene of mitochondrial complex I alter stability of the splice variants.
The effect on the stability of alternative transcripts of different mutations of the NDUFS4 gene in patients with Leigh syndrome with complex I deficiency is presented. Normally, two NDUFS4 splice variants are degraded by nonsense mediated mRNA decay (NMD) while a third form does not trigger NMD degradation. In a patient with a premature termination codon in exon 1, all the three splice variants are up-regulated. The present is the first case of a nonsense mutation leading to the abrogation of NMD, which can represent an additional event to be considered in the evaluation of clinically relevant mutations.
Department of Medical Biochemistry and Medical Biology, University of Bari, Piazza G. Cesare, Bari 70124, Italy.
Vittoria
V
Petruzzella
Damiano
D
Panelli
Alessandra
A
Torraco
Alessandro
A
Stella
Sergio
S
Papa
D017398:Alternative Splicing; D002478:Cells, Cultured; D018389:Codon, Nonsense / Q000235:genetics*; D042967:Electron Transport Complex I / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007888:Leigh Disease / Q000235:genetics*; D009154:Mutation; D009245:NADH Dehydrogenase; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics*; D014176:Protein Biosynthesis / Q000235:genetics; D020871:RNA Stability; D014158:Transcription, Genetic
D018389:Codon, Nonsense; D009247:NADH, NADPH Oxidoreductases; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I; C427643:NDUFS4 protein, human