Discovery of a Major D-Loop Replication Origin Reveals Two Modes of Human mtDNA Synthesis

Fish, Jennifer L.; Raule, Nicola; Attardi, Giuseppe

doi:10.1126/science.1102077

Cited by 111 publications

(75 citation statements)

References 23 publications

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“…5B; Table S6 in the supplemental material). In the case of the L strand, most of the ESTs were located in the vicinity of the origin of the H-strand DNA replication point, where the triple-stranded structure of the D loop begins (8,9,25,29). These ESTs are probably derived from transcription initiation at the L-strand promoter and represent cleaved molecules that serve as primers for H-strand replication.…”

Section: Resultsmentioning

confidence: 99%

Polyadenylation and Degradation of Human Mitochondrial RNA: the Prokaryotic Past Leaves Its Mark

Slomovic¹,

Laufer

Geiger

et al. 2005

Molecular and Cellular Biology

156

162

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RNA polyadenylation serves a purpose in bacteria and organelles opposite from the role it plays in nuclear systems. The majority of nucleus-encoded transcripts are characterized by stable poly(A) tails at their mature 3 ends, which are essential for stabilization and translation initiation. In contrast, in bacteria, chloroplasts, and plant mitochondria, polyadenylation is a transient feature which promotes RNA degradation. Surprisingly, in spite of their prokaryotic origin, human mitochondrial transcripts possess stable 3-end poly(A) tails, akin to nucleus-encoded mRNAs. Here we asked whether human mitochondria retain truncated and transiently polyadenylated transcripts in addition to stable 3-end poly(A) tails, which would be consistent with the preservation of the largely ubiquitous polyadenylation-dependent RNA degradation mechanisms of bacteria and organelles. To this end, using both molecular and bioinformatic methods, we sought and revealed numerous examples of such molecules, dispersed throughout the mitochondrial genome. The broad distribution but low abundance of these polyadenylated truncated transcripts strongly suggests that polyadenylationdependent RNA degradation occurs in human mitochondria. The coexistence of this system with stable 3-end polyadenylation, despite their seemingly opposite effects, is so far unprecedented in bacteria and other organelles.

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Section: Resultsmentioning

confidence: 99%

Polyadenylation and Degradation of Human Mitochondrial RNA: the Prokaryotic Past Leaves Its Mark

Slomovic¹,

Laufer

Geiger

et al. 2005

Molecular and Cellular Biology

156

162

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“…The other two mtDNA points mutations were identified in the mtDNA initiation replication site at nucleotide 57 (58 insertion C; Fig. 2) [32] and at the "hot spot" cytidine-rich D300-310 segment 303:315 C(7-8)TC(6) (Fig. 2) [33].…”

Section: Resultsmentioning

confidence: 99%

Part II. Mitochondrial mutational status of high nitric oxide adapted cell line BT-20 (BT-20-HNO) as it relates to human primary breast tumors

et al. 2012

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“…Conplastic strains of rats with identical nuclear genomes but divergent mitochondrial genomes might be a useful tool to elucidate the relationship between mtDNA variants and metabolic phenotypes [22]. A recent study suggested that human cells exhibit two modes of mtDNA replication: one is a maintenance mode, regulated at the origin at np 57, which is mainly responsible for maintaining the mtDNA copy number under steady-state conditions; the other is an induced mode, regulated at the origins and at the premature termination site at the 3′ end of the D-loop, which plays a major role in the initial recovery following mtDNA depletion [23]. Thus, it is possible that the different mtSSB binding affinities for the 16189 region change the rate of premature termination, thereby altering the speed of recovery following mtDNA damage.…”

Section: Discussionmentioning

confidence: 99%

A mitochondrial DNA variant at position 16189 is associated with type 2 diabetes mellitus in Asians

et al. 2008

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Aims/hypothesis This multinational study was conducted to investigate the association between a mitochondrial DNA (mtDNA) T16189C polymorphism and type 2 diabetes in Asians. The mtDNA 16189C variant has been reported to be associated with insulin resistance and type 2 diabetes. However, a recent meta-analysis concluded that it is negatively associated with type 2 diabetes in Europids. Since the phenotype of an mtDNA mutant may be influenced by environmental factors and ethnic differences in the nuclear and mitochondrial genomes, we investigated the association between the 16189C variant and type 2 diabetes in Asians. Methods The presence of the mtDNA 16189C variant was determined in 2,469 patients with type 2 diabetes and 1,205

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Discovery of a Major D-Loop Replication Origin Reveals Two Modes of Human mtDNA Synthesis

Cited by 111 publications

References 23 publications

Polyadenylation and Degradation of Human Mitochondrial RNA: the Prokaryotic Past Leaves Its Mark

Polyadenylation and Degradation of Human Mitochondrial RNA: the Prokaryotic Past Leaves Its Mark

Part II. Mitochondrial mutational status of high nitric oxide adapted cell line BT-20 (BT-20-HNO) as it relates to human primary breast tumors

A mitochondrial DNA variant at position 16189 is associated with type 2 diabetes mellitus in Asians

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