The regulation of PTC containing transcripts of the human NDUFS4 gene of complex I of respiratory chain and the impact of pathological mutations.
The regulation of alternative transcripts of the NDUFS4 gene of complex I of the respiratory chain has been studied in human cell lines. One of the alternative transcripts (SV1) is subjected to the NMD degradation pathway which involves the hUPF1 and hUPF2 factors. Another transcript (SV3) appears to be controlled in the nuclear fraction and to be enhanced when hUPF1 is depleted, but unaffected by translation inhibitors or when hUPF2 expression is down-regulated. A pathological homozygous nonsense mutation in exon 1, found in a patient affected by mitochondrial disorder, inactivated in the patient's fibroblasts NMD degradation of SV1 and enhanced the nuclear production of SV3. In another patient with a homozygous splice acceptor site mutation in intron 1, SV3, which was the only transcript of NDUFS4 gene to be produced, accumulated in fibroblasts.
Panelli
Damiano
D
Institute of Biomembranes and Bioenergetics, Italian Research Council, Bari, Italy.
Petruzzella
Vittoria
V
Vitale
Rita
R
De Rasmo
Domenico
D
Munnich
Arnold
A
Rötig
Agnès
A
Papa
Sergio
S
D017398:Alternative Splicing; D002467:Cell Nucleus / Q000235:genetics; D018389:Codon, Nonsense / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation; D004579:Electron Transport; D042967:Electron Transport Complex I; D005091:Exons / Q000235:genetics; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D007438:Introns / Q000235:genetics; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics*; D014176:Protein Biosynthesis; D020871:RNA Stability
D018389:Codon, Nonsense; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I; C427643:NDUFS4 protein, human