Functional and structural features of a tandem duplication of the human mtDNA promoter region.
An approximately 260-bp tandem duplication of the human mtDNA regulatory region has been identified in patients with mitochondrial disorders and in a specific Caucasian haplogroup. The functional significance of this mtDNA duplication was difficult to assess, because it was present at very low levels in human tissues. We have isolated several transmitochondrial cybrid lines harboring this mutation, one of which (clone CA17.1) was essentially homoplasmic for the duplication. Oxidative-phosphorylation function was not impaired in clone CA17.1, suggesting that this mtDNA alteration is not pathogenic. mtDNA copy number and steady-state levels of heavy- and light-strand transcripts were unaltered in clone CA 17.1. The steady-state levels of RNAs made from the two promoters (either from the heavy-strand or from the light-strand) were also similar, indicating that oppositely oriented promoters did not interfere with each other.
Hao
H
H
Department of Neurology, University of Miami, FL, USA.
Manfredi
G
G
Moraes
C T
CT
D001483:Base Sequence; D002999:Clone Cells; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D012516:Osteosarcoma; D010085:Oxidative Phosphorylation; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012356:RNA, Transfer, Leu / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D044465:White People / Q000235:genetics
D004272:DNA, Mitochondrial; D012356:RNA, Transfer, Leu