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PMID:17662942

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Citation

Park, CB, Asin-Cayuela, J, Cámara, Y, Shi, Y, Pellegrini, M, Gaspari, M, Wibom, R, Hultenby, K, Erdjument-Bromage, H, Tempst, P, Falkenberg, M, Gustafsson, CM and Larsson, NG (2007) MTERF3 is a negative regulator of mammalian mtDNA transcription. Cell 130:273-85

Abstract

Regulation of mammalian mtDNA gene expression is critical for altering oxidative phosphorylation capacity in response to physiological demands and disease processes. The basal machinery for initiation of mtDNA transcription has been molecularly defined, but the mechanisms regulating its activity are poorly understood. In this study, we show that MTERF3 is a negative regulator of mtDNA transcription initiation. The MTERF3 gene is essential because homozygous knockout mouse embryos die in midgestation. Tissue-specific inactivation of MTERF3 in the heart causes aberrant mtDNA transcription and severe respiratory chain deficiency. MTERF3 binds the mtDNA promoter region and depletion of MTERF3 increases transcription initiation on both mtDNA strands. This increased transcription initiation leads to decreased expression of critical promoter-distal tRNA genes, which is possibly explained by transcriptional collision on the circular mtDNA molecule. To our knowledge, MTERF3 is the first example of a mitochondrial protein that acts as a specific repressor of mammalian mtDNA transcription initiation in vivo.

Links

PubMed Online version:10.1016/j.cell.2007.05.046

Keywords

Animals; DNA, Mitochondrial/genetics; Down-Regulation/genetics; Electron Transport; Embryo, Mammalian/metabolism; Embryonic Development; Gene Targeting; Genes, Essential; HeLa Cells; Humans; Mice; Mice, Knockout; Mitochondria/pathology; Mitochondrial Proteins/metabolism; Myocardium/pathology; Myocardium/ultrastructure; Organ Specificity; Phenotype; Promoter Regions, Genetic/genetics; Protein Binding; RNA, Messenger/genetics; RNA, Messenger/metabolism; Transcription Factors/metabolism; Transcription, Genetic

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:MTEF3

involved_in

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MTEF3

located_in

GO:0005739: mitochondrion

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:MTEF3

involved_in

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MTEF3

enables

GO:0000976: transcription regulatory region sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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