Mammalian mitochondrial D-loop region structural analysis: identification of new conserved sequences and their functional and evolutionary implications

Sbisà, Elisabetta; Tanzariello, F.; Reyes, Aurelio; Pesole, Graziano; Saccone, Cecilia

doi:10.1016/s0378-1119(97)00404-6

Cited by 458 publications

(421 citation statements)

References 31 publications

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“…LSP was mapped between 16183bp and inside region of the tRNA pro [16,33,35 ]. These results of the in-vitro generated transcription products presented in this study are also in good agreement with the previous reports [13,17,20,30] of the in-vivo transcription initiation products from the HSP/LSP containing the mt D-loop region spanning at one end of tRNA leu and the other end of tRNA thr .…”

Section: Discussionsupporting

confidence: 92%

“…210bp(L), 164bp(H) and 94bp(H) from p405 construct, >210bp(L) and >150bp(L) from p622 construct and 94bp(H) from p10 constructs. These results were in good agreement with the previously reported sizes (ranging between >100bp and >700bp) for both human and mouse mitochondrial D-loop segment [13,17,20,27,32,33]. The D-loop distal mitochondrial DNA segment (15330bp-11970bp) cloned in both orientations in pT71 and pT72 vectors lacked the D-loop region (LSP/ HSP major and minor promoters) and failed to initiate transcription in-vitro reconstituted transcription system as evidenced both by nitrocellulose-filter-binding assay for radioactive incorporation counting in liquid-based scintillation fluid and 3.5% sequencing gel analysis of the initiation products.…”

supporting

confidence: 93%

“…By S1 nuclease protection assay, the identification of 5′capped RNA, Northern blot with the specific DNA probes, hybridization of the pulse-labeled RNA to the cellulose-linked DNA, analysis of protein synthesis of the mt specific proteins in the submitochondrial fractions or the mitochondrial lysate, the mouse mt HSP was mapped between 16216bp and 16276bp [16,33,35]. LSP was mapped between 16183bp and inside region of the tRNA pro [16,33,35 ].…”

Section: Discussionmentioning

confidence: 99%

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3D model of RNA polymerase and bidirectional transcription

Bhattacharya

2007

Biochemical and Biophysical Research Communications

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In the in-vitro mitochondrial (mt) transcription initiation system with mt RNA polymerase fraction and mt lysate, the transcription initiation products were shown to be synthesized bi-directionally from the only H-strand-promoter (HSP)/L-strand-promoter region (LSP) of the mitochondrial Dloop genome segment. These transcription products ranged between >100bp and >800bp with the purified mitochondrial RNA polymerase fraction, but were larger (>2030bp-4000bp) in size with the mitochondrial lysate in both human and mouse [references 1-20]. In this brief report, an invitro reconstituted mitochondrial transcription system purified by affinity chromatography (heparinsepharose) from mouse hypotetraploid letter Ehrlich ascites tumor cell mitochondria was shown to initiate transcription bidirectionally from the mitochondrial D-loop region (HSP/LSP), as evidenced by in-vitro generated transcription products. The in-vitro generated transcription products were separated by sequencing gel. But this in-vitro reconstituted transcription system was not studied beyond the D-loop region. A 3D model of the enzyme RNA polymerase was docked with both ATP and CTP. KeywordsMitochondrial D-loop region; In-vitro transcription; mt RNA polymerase; gel-mobility shift assay; 3D model Both human and mouse mitochondrial (mt) in-vitro reconstituted transcription system and mt lysate were shown to transcribe bidirectionally from D-loop region containing H-strandpromoter/L-strand-promoter (HSP/LSP) of mitochondrial genome .These transcripts ranged between >100bp and >3000bp in both human and mouse [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. The D-loop distal genes were also transcribed in this system [16]. The nuclear coded RNA polymerase, RNase P and RNase MRP as well as several transcription factors have now been proposed to function in a co-ordinate fashion for the synthesis of the polycistronic RNA and its processing into individual RNA molecules [1][2][3][4][5][6][7][8][9][10][11][12]. The ideal human transcription complex [13] was described to constitute RNA polymerase, transcription factor TFB1M (or TFB2M having weaker activity than TFB2M), LSP/HSP template (1-741bp) and mt general transcription factor TFAM. The mouse homologs (or orthologs) mTfb1m and mTfb2m were identified [13]. The transcription termination was reported to occur by 34kd mt-TERM/mtTERF DNA binding protein [14,15], although 24kd Tf1 transcription factor, 48kd TAS-A protein (which binds to termination associated sequence of mt D-loop region) as well as other putative binding proteins (TAS-B, -C, -D, -E, -F, -G; A/B and F/G which bind to partially overlapping sites) in the mt D-loop segment were reported [15,16]. Two-to-three putative mitochondrial transcription termination 1 Corresponding author: Pradip Bhattacharya, Room Nos. 121, School of Life Sciences, Jawaharlal Nehru University, New Delhi-110067, India. Fax: 91-11-26165886; Tel: 91-11-26704529, Email address: ronaldraegon@yahoo.com Publisher's Disclaimer: This is a PDF file o...

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Section: Discussionsupporting

confidence: 92%

supporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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3D model of RNA polymerase and bidirectional transcription

Bhattacharya

2007

Biochemical and Biophysical Research Communications

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“…Replication of insect mtDNA is extremely asymmetric. Since the structure of the control region in mammals/chordates (Sbisá et al, 1997;Saccone et al, 1991) and insects (Saito et al, 2005;Zhang and Hewitt, 1997) is very different it is unclear at present whether the same mechanisms are responsible for initiation and termination of replication throughout the Metazoa.…”

Section: Model(s) Of Replicationmentioning

confidence: 99%

“…This situation appears to be largely conserved throughout the vertebrates (Coucheron et al, 2011). The box II sequence itself is conserved at least throughout the mammals (Sbisá et al, 1997). In Drosophila, RNA synthesis starts at two promoters on the heavy (H) strand and three on the light (L) strand, largely matching the alternating blocks of genes located on heavy and light strand, respectively (Berthier et al, 1986;Torres et al, 2009).…”

Section: Transcriptomementioning

confidence: 99%

Genetic aspects of mitochondrial genome evolution

Bernt

Braband

Schierwater

et al. 2013

Molecular Phylogenetics and Evolution

227

148

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Mitochondrial DNA control region sequence variation in migraine headache and cyclic vomiting syndrome

Wang

Ito

Adams

et al. 2004

American J of Med Genetics Pt A

106

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Migraine headache is a very common condition affecting about 10% of the population that results in substantial morbidity and economic loss. The two most common variants are migraine with (MA) and without (MO) aura. Often considered to be a migraine-like variant, cyclic vomiting syndrome (CVS) is a predominately childhood condition characterized by severe, discrete episodes of nausea, vomiting, and lethargy. Disease-associated mitochondrial DNA (mtDNA) sequence variants are suggested in common migraine and CVS based upon a strong bias towards the maternal inheritance of disease, and several other factors. Temporal temperature gradient gel electrophoresis (TTGE) followed by cyclosequencing and RFLP was used to screen almost 90% of the mtDNA, including the control region (CR), for heteroplasmy in 62 children with CVS and neuromuscular disease (CVS+) and in 95 control subjects. One or two rare mtDNA-CR heteroplasmic sequence variants were found in six CVS+ and in zero control subjects (P = 0.003). These variants comprised 6 point and 2 length variants in hypervariable regions 1 and 2 (HV1 and HV2, both part of the mtDNA-CR), one half of which were clustered in the nt 16040-16188 segment of HV1 that includes the termination associated sequence (TAS), a functional location important in the regulation of mtDNA replication. Based upon our findings, sequencing and statistical analysis looking for homoplasmic nucleotide changes was performed in HV1 among 30 CVS+, 30 randomly-ascertained CVS (rCVS), 18 MA, 32 MO, and 35 control haplogroup H cases. Within the nt 16040-16188 segment, homoplasmic sequence variants were three-fold more common relative to control subjects in both CVS groups (P = 0.01 combined data) and in MO (P = 0.02), but not in MA (P = 0.5 vs. control subjects and 0.02 vs. MO). No group differences were noted in the remainder of HV1. We conclude that sequence variation in this small "peri-TAS" segment is associated with CVS and MO, but not MA. These variants likely constitute risk factors for disease development. Our findings are consistent with previous data demonstrating progression of CVS into MO in many cases, and the co-segregation in a maternal inheritance pattern of CVS and MO within families. A mitochondrial component in the pathogenesis of migraine and CVS has therapeutic implications, especially concerning the avoidance of fasting.

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Mammalian mitochondrial D-loop region structural analysis: identification of new conserved sequences and their functional and evolutionary implications

Cited by 458 publications

References 31 publications

3D model of RNA polymerase and bidirectional transcription

3D model of RNA polymerase and bidirectional transcription

Genetic aspects of mitochondrial genome evolution

Mitochondrial DNA control region sequence variation in migraine headache and cyclic vomiting syndrome

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