Transcription from mitochondrial promoters (Homo sapiens)

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2-4, 6-815, 9mitochondrial matrixTFAM mitochondrial DNApromotermitochondrial DNA promoter TFAM:mitochondrialpromoter complexPOLRMT:TFB2M complexTFB2M MTERF MTERFTFAM TFB2M mitochondrialtranscriptionterminationsequencePOLRMT:TFB2M:TFAM:mitochondrial promoter complexmitochondrial DNA promoter TFAMmitochondrial transcription termination sequence POLRMT POLRMT mTERF:mitochondrialtranscriptionterminationsequence


Description

Thirteen of the ~80 different proteins present in the respiratory chain of human mitochondria are encoded by the mitochondrial genome (mtDNA). The circular mtDNA, which is present in 1000 to 10000 copies in the human cell, also encodes for 2 ribosomal RNAs, and 22 transfer RNAs. The double-stranded mitochondrial genome lacks introns and the longer non-coding region contains the control elements for transcription and replication of mtDNA (Shadel and Clayton, 1997). The two mtDNA strands are referred to as the heavy (H-strand) and the light (L-strand) due to their differing G+T content. In human cells, each strand contains one single promoter for transcriptional initiation, the light-strand promoter (LSP) or the heavy-strand promoter (HSP). Transcription from the mitochondrial promoters produce polycistronic precursor RNA encompassing all the genetic information encoded in each of the specific strands. The primary transcripts are processed to produce the individual tRNA and mRNA molecules (Clayton, 1991; Ojala et al., 1981). There is likely a second initiation site for heavy strand transcription, which produces RNAs spanning the rDNA region. The resulting transcript including the genes for the two mitochondrial rRNAs and ends at the boundary between the 16 S rRNA and the tRNALeu(UUR) genes (Montoya et al., 1982; Montoya et al.,1983; Christianson and Clayton 1986). The existence of such a separate transcription unit may explain why the steady-state levels of rRNAs are much higher than the steady state levels of mRNAs. View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 75944
Reactome-version 
Reactome version: 65
Reactome Author 
Reactome Author: Gustafsson, CM

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Bibliography

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  1. Fisher RP, Topper JN, Clayton DA.; ''Promoter selection in human mitochondria involves binding of a transcription factor to orientation-independent upstream regulatory elements.''; PubMed Europe PMC Scholia
  2. Clayton DA.; ''Replication and transcription of vertebrate mitochondrial DNA.''; PubMed Europe PMC Scholia
  3. Montoya J, Gaines GL, Attardi G.; ''The pattern of transcription of the human mitochondrial rRNA genes reveals two overlapping transcription units.''; PubMed Europe PMC Scholia
  4. Ojala D, Montoya J, Attardi G.; ''tRNA punctuation model of RNA processing in human mitochondria.''; PubMed Europe PMC Scholia
  5. Shadel GS, Clayton DA.; ''Mitochondrial DNA maintenance in vertebrates.''; PubMed Europe PMC Scholia
  6. Christianson TW, Clayton DA.; ''In vitro transcription of human mitochondrial DNA: accurate termination requires a region of DNA sequence that can function bidirectionally.''; PubMed Europe PMC Scholia
  7. Montoya J, Christianson T, Levens D, Rabinowitz M, Attardi G.; ''Identification of initiation sites for heavy-strand and light-strand transcription in human mitochondrial DNA.''; PubMed Europe PMC Scholia
  8. Gaspari M, Falkenberg M, Larsson NG, Gustafsson CM.; ''The mitochondrial RNA polymerase contributes critically to promoter specificity in mammalian cells.''; PubMed Europe PMC Scholia
  9. Falkenberg M, Gaspari M, Rantanen A, Trifunovic A, Larsson NG, Gustafsson CM.; ''Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
115097view17:04, 25 January 2021ReactomeTeamReactome version 75
113539view12:01, 2 November 2020ReactomeTeamReactome version 74
112736view16:14, 9 October 2020ReactomeTeamReactome version 73
101652view11:51, 1 November 2018ReactomeTeamreactome version 66
101188view21:39, 31 October 2018ReactomeTeamreactome version 65
100715view20:11, 31 October 2018ReactomeTeamreactome version 64
100265view16:57, 31 October 2018ReactomeTeamreactome version 63
99818view15:21, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99358view12:48, 31 October 2018ReactomeTeamreactome version 62
93265view11:18, 9 August 2017ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
MTERF ProteinQ99551 (Uniprot-TrEMBL)
MTERFProteinQ99551 (Uniprot-TrEMBL)
POLRMT ProteinO00411 (Uniprot-TrEMBL)
POLRMT:TFB2M complexComplexR-HSA-163306 (Reactome)
POLRMT:TFB2M:TFAM:mitochondrial promoter complexComplexR-HSA-163307 (Reactome)
TFAM ProteinQ00059 (Uniprot-TrEMBL)
TFAM:mitochondrial promoter complexComplexR-HSA-163298 (Reactome)
TFAMProteinQ00059 (Uniprot-TrEMBL)
TFB2M ProteinQ9H5Q4 (Uniprot-TrEMBL)
mTERF:mitochondrial

transcription termination

sequence
ComplexR-HSA-163321 (Reactome)
mitochondrial

transcription termination

sequence
R-ALL-164569 (Reactome)
mitochondrial DNA promoterR-ALL-163305 (Reactome)
mitochondrial DNA promoter R-ALL-163305 (Reactome)
mitochondrial transcription termination sequence R-ALL-164569 (Reactome)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
MTERFR-HSA-163320 (Reactome)
POLRMT:TFB2M complexR-HSA-163296 (Reactome)
POLRMT:TFB2M:TFAM:mitochondrial promoter complexArrowR-HSA-163296 (Reactome)
R-HSA-163296 (Reactome) At the beginning of this reaction, 1 molecule of 'POLRMT:TFB2M complex', and 1 molecule of 'TFAM:mitochondrial promoter complex' are present. At the end of this reaction, 1 molecule of 'POLRMT:TFB2M:TFAM:mitochondrial promoter complex' is present.

This reaction takes place in the 'mitochondrial matrix'.

R-HSA-163310 (Reactome) Studies of human LSP have revealed that a minimal DNA fragment corresponding to position -28 to +16 relative to the transcription initiation site is able to support transcription initiation in a mitochondrial extract (Chang and Clayton, 1984). TFAM interacts directly with nucleotides between positions -35 and -17 (Fisher et al., 1987), and the exact distance between the TFAM-binding site and the transcription start site is essential for promoter activity (Dairaghi et al., 1995).
R-HSA-163320 (Reactome) The 39-kDa mitochondrial transcription termination factor (mTERF), binds to a 28-base pair region of mtDNA (3237-3249) located within the tRNALeu(UUR) gene, at a position immediately downstream of the rRNA 16S gene (Fernandez-Silva et al., 1997; Kruse et al., 1989; Daga et al., 1993). mTERF binding to the termination sequence block transcription bidirectionally in a partially purified human mitochondrial system (Shang and Clayton, 1994). A polar termination activity has been also observed for the sea urchin homologue of mTERF, referred to as mtDBP with respect of phage RNA polymerases (Fernandez Silva et al. 2001).
TFAM:mitochondrial promoter complexArrowR-HSA-163310 (Reactome)
TFAM:mitochondrial promoter complexR-HSA-163296 (Reactome)
TFAMR-HSA-163310 (Reactome)
mTERF:mitochondrial

transcription termination

sequence
ArrowR-HSA-163320 (Reactome)
mitochondrial

transcription termination

sequence
R-HSA-163320 (Reactome)
mitochondrial DNA promoterR-HSA-163310 (Reactome)
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