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Results for “mtDNA editing”

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7 recordsLinked to original sources
PubMed2026

Single-cell profiling of mitochondrial phenotyping-coupled mtDNA genotyping.

Simultaneously profiling mitochondrial DNA (mtDNA) heteroplasmy and phenotypic variability at the single-cell level remains a challenge due to the absence of integrated methods that map mitochondrial genotypes alongside their functional states. We introduce human single-cell mitochondrial phenotype-coupled mtDNA sequencing (scMPCDS), a platform that quantifies mtDNA mutations and heteroplasmy together with mitochondrial membrane potential and reactive oxygen species within individual cells. Unlike bulk sequencing or separate single-omics techniques, scMPCDS directly correlates mitochondrial genomic instability with functional outcomes. Using this approach, we demonstrate that DdCBE-mediated mtDNA editing induces cell-specific off-target mutations in the mitochondrial genome, which coincide with diverse phenotypic changes. Applying scMPCDS to HeLa cells and clear cell renal cell carcinoma tissues, we identify single-cell subpopulations exhibiting distinct mtDNA mutation burdens and altered bioenergetic profiles, implicating potential mitochondrial heterogeneity-driven tumor evolution. Overall, scMPCDS serves as a versatile tool to unravel mitochondrial genotype-phenotype relationships at the single-cell level in both normal and disease states, thereby advancing precise mitochondrial diagnostics and therapeutics.

Humans↗
PubMed1992

Silent mitochondrial and active nuclear genes for subunit 2 of cytochrome c oxidase (cox2) in soybean: evidence for RNA-mediated gene transfer.

In most plants and other eukaryotes investigated, the mitochondrial genome carries the gene encoding subunit 2 of cytochrome c oxidase (cox2). In this paper, we show that the previously reported mitochondrial cox2 of soybean is actually silent, and that there is an expressed, single-copy, nucleus-encoded cox2. Molecular cloning and sequence analysis of cox2 cDNA and genomic clones show that the soybean nuclear gene encodes an N-terminal extension that resembles a signal sequence for mitochondrial import and whose coding sequence is separated by an intron from that corresponding to mtDNA-encoded cox2. Comparison of soybean mitochondrial and nuclear cox2 sequences clearly indicates that in an ancestor of soybean, cox2 was transferred from the mitochondrion to the nucleus via a C-to-U edited RNA intermediate.

Amino Acid Sequence↗
PubMed1991

The cytochrome oxidase II gene in mitochondria of the sugar-beet Beta vulgaris L.

We have cloned and analyzed the sugar-beet mitochondrial gene for cytochrome oxidase subunit II (coxII). The sugar-beet and its deduced amino acid sequence were compared to its homologous coxII gene sequences from both monocot and dicot plants. It was found to be highly conserved (89-95%) compared to homologue in other plant species. The 780 bp coding sequence of the sugar beet coxII gene is interrupted at position 383 by a 1463 bp intron. This intron contains an additional 107 bp sequence that is not found in any of the plant coxII genes studied thus far. The structure of the intron suggests that a large intron existed in an ancestral coxII gene before monocots and dicots diverged in evolution. Three CGG codons in the sugar-beet coxII coding sequence align with conserved tryptophan residues in the homologous gene of other species, suggesting that RNA editing takes place also in sugar-beet mitochondria. In 13 out of 24 codons of coxII mRNA that were found to be edited in four other plants, the sugar-beet gene already utilizes the edited codons. This phenomenon may indicate that the mitochondrial genome in sugar-beet is phylogenetically more archaic relative to these plants. An additional sequence of 279 bp that is identical to the first exon of coxII was identified in the mtDNA of the sugar-beet. This 'pseudo-gene' is transcribed and its existence in the mitochondrial genome is unexplained.

Amino Acid Sequence↗
PubMed1992

The coxII gene in carrot mitochondria contains two introns.

The gene for cytochrome oxidase subunit II (coxII) in carrot is encoded by a unique locus in the mitochondrial genome. In contrast to the coxII genes in the numerous other plant species investigated to date, the coding region is interrupted by two group II introns. The carrot 5' intron is the homologue of the single intervening sequence found in several monocot and dicot coxII genes. Sequences similar to the 3' intron of the carrot coxII gene have not been reported previously and are not detectable by hybridization with Oenothera mtDNA. Northern hybridizations indicate complex precursor transcript patterns with mRNA molecules up to 10 kb length. The excised intron sequences appear to be stably maintained in the mRNA pool. Amino acid sequence comparisons suggest that the carrot coxII mRNA needs to be edited by numerous C to U transitions.

Amino Acid Sequence↗
PubMed2023

Polγ coordinates DNA synthesis and proofreading to ensure mitochondrial genome integrity.

Accurate replication of mitochondrial DNA (mtDNA) by DNA polymerase γ (Polγ) is essential for maintaining cellular energy supplies, metabolism, and cell cycle control. To illustrate the structural mechanism for Polγ coordinating polymerase (pol) and exonuclease (exo) activities to ensure rapid and accurate DNA synthesis, we determined four cryo-EM structures of Polγ captured after accurate or erroneous incorporation to a resolution of 2.4-3.0 Å. The structures show that Polγ employs a dual-checkpoint mechanism to sense nucleotide misincorporation and initiate proofreading. The transition from replication to error editing is accompanied by increased dynamics in both DNA and enzyme, in which the polymerase relaxes its processivity and the primer-template DNA unwinds, rotates, and backtracks to shuttle the mismatch-containing primer terminus 32 Å to the exo site for editing. Our structural and functional studies also provide a foundation for analyses of Polγ mutation-induced human diseases and aging.

Humans↗
PubMed1991

The rice mitochondrial nad3 gene has an extended reading frame at its 5' end: nucleotide sequence analysis of rice trnS, nad3, and rps12 genes.

The nucleotide sequences of the tRNASer (trnS), pseudo-tRNA, NADH dehydrogenase subunit 3 (nad3), and ribosomal protein S12 (rps12) genes from rice mitochondrial DNA (mtDNA) were determined. Both trnS and nad3 were confirmed to be single copy genes by Southern blot analysis. The nad3 and rps12 genes were arranged in tandem, and the two were co-transcribed. The order of the above four genes in rice mtDNA differed from the linear order observed for the wheat and maize genes. In rice mitochondria, the trnS and pseudo-tRNA genes were found upstream of the cytochrome c oxidase subunit I gene, instead of the nad3 and rps12 genes as observed in maize and wheat. Additionally, while the rice nad3 and rps12 genes remain paired, they too are in a different sequence environment from the wheat and maize genes. The apparent split of the two pairs of genes indicates the occurrence of a mitochondrial intramolecular recombinational event. Another peculiarity is that the sequence upstream of the translational initiation codon of the rice nad3 gene is different from that of the wheat and maize versions. The ATG initiation codon of wheat and maize nad3 is replaced by TTG in the rice nad3. A subsequent deduction of the amino acid sequence, accompanied by a primer extension analysis, indicates that the predicted rice NAD3 protein has an additional 37 amino acid residues at its N-terminus compared to the wheat and maize NAD3 proteins. cDNA sequence analysis showed no introns or the occurrence of RNA editing at the newly replaced TTG codon.

Amino Acid Sequence↗
PubMed1990

A set of tRNAs that lack either the T psi C arm or the dihydrouridine arm: towards a minimal tRNA adaptor.

The mitochondrial DNA (mtDNA) molecules of the nematode worms, Caenorhabditis elegans and Ascaris suum contain 22 putative genes for non-standard forms of tRNAs. The inferred transcripts can be folded into 20 separate structures each resembling a tRNA whose T psi C arm and variable loop are replaced with a simple loop of 6-12 nucleotides. In two further structures [that resemble tRNAs for ser(UCN) and ser(AGN)], the dihydrouridine arm is replaced by a loop of 5-8 nucleotides. By hybridizing mt-tRNA gene-specific oligonucleotide probes to nematode RNAs, we have obtained evidence for transcription of at least nine C.elegans and three A.suum mt-tRNA genes. Each transcript (tRNA) is the exact size predicted from the respective DNA sequence, to which three nucleotides, presumably CCA, have been added following transcription. An exception was C.elegans mt-tRNAasn, most molecules of which had one nucleotide (plus CCA) more than predicted from the gene. The data presented strongly support the conclusion that the functional mt-tRNAs of nematode worms are direct transcripts (with only CCA addition) of the structurally unusual mt-tRNA genes. There is no evidence of trans-splicing or RNA editing to add the sequences missing from these nonstandard tRNAs. We presume, therefore, that the non-standard forms are active in mitochondrial protein synthesis.

Animals↗