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.
Petruzzella
Vittoria
V
Department of Medical Biochemistry and Medical Biology, University of Bari, Piazza G. Cesare, Bari 70124, Italy.
Panelli
Damiano
D
Torraco
Alessandra
A
Stella
Alessandro
A
Papa
Sergio
S
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