ArticleProceedings of the National Academy of Sciences of the United States of America2012
Transcriptional requirements of the distal heavy-strand promoter of mtDNA.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 55 citations in OpenAlex.
- Mitochondria-targeted gene delivery using fluorinated lipid nanoparticles to alleviate Leber's hereditary optic neuropathy.Nature communications · 2025Article
- Mitochondrial DNA copy number alterations: Key players in the complexity of glioblastoma (Review).Molecular medicine reports · 2025Review
- Mitochondrial DNA transcription and mitochondrial genome-encoded long noncoding RNA in diabetic retinopathy.Mitochondrion · 2024Article
- Mechanisms and pathologies of human mitochondrial DNA replication and deletion formation.The Biochemical journal · 2024Review
- Mechanisms and regulation of human mitochondrial transcription.Nature reviews. Molecular cell biology · 2024Review
- 35 Years of TFAM Research: Old Protein, New Puzzles.Biology · 2023Review
- The human mitochondrial genome contains a second light strand promoter.Molecular cell · 2022Article
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- A minimal motif for sequence recognition by mitochondrial transcription factor A (TFAM).Nucleic acids research · 2022Article
- Dynamic features of human mitochondrial DNA maintenance and transcription.Frontiers in cell and developmental biology · 2022Review
- Structure, mechanism, and regulation of mitochondrial DNA transcription initiation.The Journal of biological chemistry · 2020Review
- Polymerase γ efficiently replicates through many natural template barriers but stalls at the HSP1 quadruplex.The Journal of biological chemistry · 2020Article
- Review
- Functional conservation of mitochondrial RNA levels despite divergent mtDNA organization.BMC research notes · 2020Article
- Mechanisms of mammalian mitochondrial transcription.Protein science : a publication of the Protein Society · 2019Review
- Differences in Liver TFAM Binding to mtDNA and mtDNA Damage between Aged and Extremely Aged Rats.International journal of molecular sciences · 2019Article
- Mitochondrial miRNA Determines Chemoresistance by Reprogramming Metabolism and Regulating Mitochondrial Transcription.Cancer research · 2019Article
- Higher Order Organization of the mtDNA: Beyond Mitochondrial Transcription Factor A.Frontiers in genetics · 2019Review
- Recent Advances in Mitochondria-Targeted Gene Delivery.Molecules (Basel, Switzerland) · 2018Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
Abstract
The heavy strand of mtDNA contains two promoters with nonoverlapping functions. The role of the minor heavy-strand promoter (HSP2) is controversial, because the promoter has been difficult to activate in an in vitro system. We have isolated HSP2 by excluding its interaction with the more powerful HSP1 promoter, and we find that it is transcribed efficiently by recombinant mtRNA polymerase and mitochondrial transcription factor B2. The mitochondrial transcription factor A is not required for initiation, but it has the ability to alternatively activate and repress the HSP2 transcriptional unit depending on the ratio between mitochondrial transcription factor A and other transcription factors. The positioning of transcriptional initiation agrees with our current understanding of HSP2 activity in vivo. Serial deletion of HSP2 shows that only proximal sequences are required. Several mutations, including the disruption of a polycytosine track upstream of the HSP2 initiation site, influence transcriptional activity. Transcription from HSP2 is also observed when HeLa cell mitochondrial extract is used as the source of mitochondrial polymerase, and this transcription is maintained when HSP2 is provided in proper spacing and context to the HSP1 promoter. Studies of the linked heavy-strand promoters show that they are differentially regulated by ATP dosage. We conclude that HSP2 is transcribed and has features that allow it to regulate mitochondrial mRNA synthesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.