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Literature summary for 2.7.7.6 extracted from
- Human mitochondrial RNA polymerase: structure-function, mechanism and inhibition (2012), Biochim. Biophys. Acta, 1819, 948-960.
Crystallization (Commentary)
| Crystallization (Comment) | Organism |
|---|---|
| crystal structure anaysis | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| additional information | POLRMT is an off target for antiviral ribonucleoside analogues, unique mechanisms of mitochondrial transcription inhibition, overview | Homo sapiens |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| mitochondrion | - |
Homo sapiens | 5739 | - |
| mitochondrion | - |
Saccharomyces cerevisiae | 5739 | - |
| additional information | the enzyme is encoded in the nucleus | Homo sapiens | - |
- |
| additional information | the enzyme is encoded in the nucleus | Saccharomyces cerevisiae | - |
- |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | two ions are required for polymerase-catalyzed nucleotide incorporation, binding structure, overview | Homo sapiens |  |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + RNAn | Homo sapiens | - |
diphosphate + RNAn+1 | - |
? | |
| nucleoside triphosphate + RNAn | Homo sapiens | - |
diphosphate + RNAn+1 | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
| Saccharomyces cerevisiae | - |
gene RPO41 | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 2'-C-methyl-ATP + RNAn | misincorporation frequency of approximately 1 in 7800 2'-C-methyl-ATP | Homo sapiens | diphosphate + RNAn+1 | - |
? | |
| 2'-deoxy-ATP + RNAn | misincorporation | Homo sapiens | diphosphate + RNAn+1 | - |
? | |
| 3'-deoxy-ATP + RNAn | misincorporation frequency of approximately 1 in 5 3'-dATP | Homo sapiens | diphosphate + RNAn+1 | - |
? | |
| ATP + RNAn | - |
Homo sapiens | diphosphate + RNAn+1 | - |
? | |
| GTP + RNAn | - |
Homo sapiens | diphosphate + RNAn+1 | - |
? | |
| nucleoside triphosphate + RNAn | - |
Homo sapiens | diphosphate + RNAn+1 | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| monomer | the enzyme consists of three distinct regions, a catalytic C-terminal polymerase domain (residues 648-1230), an N-terminal domain (residues 369-647) and an N-terminal extension (residues 1-368), domain architecture, overview. The POLRMT C-terminal domain is characteristic of the Pol I family of nucleic acid polymerases, typically described as resembling the shape of a cupped right hand, containing the fingers, palm and thumb subdomains. The palm subdomain contains several key structural motifs that are highly conserved among the different classes of nucleic acid polymerases. The N-terminal extension contains the mitochondrial targeting sequence (residues 1-41), a large, flexible region of unknown structure (residues 42-217) and a pentatricopeptide repeat domain (residues 218-368). The pentatricopeptide repeat domain is connected to the N-terminal domain via a short proline-rich linker region that likely functions as a spacer connecting the two domains. The pentatricopeptide repeat domain consists of two tandem PPR motifs, the domnain contains nine alpha-helices of which four comprise the pentatricopeptide repeat motifs | Homo sapiens |
| More | the enzyme consists of three distinct regions, a catalytic C-terminal polymerase domain, an N-terminal domain and an N-terminal extension, a pentatricopeptide repeat domain is not present in the yeast enzyme | Saccharomyces cerevisiae |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| h-mtRNAP | - |
Homo sapiens |
| mitochondrial RNA polymerase | - |
Homo sapiens |
| mitochondrial RNA polymerase | - |
Saccharomyces cerevisiae |
| mtRNAP | - |
Saccharomyces cerevisiae |
| POLRMT | - |
Homo sapiens |
| Rpo41 | - |
Saccharomyces cerevisiae |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | human mitochondrial RNA polymerase is distantly related to the bacteriophage T7 class of single-subunit RNAPs with a probably similar mechanisms for nucleotide binding, substrate selection and catalysis/nucleotidyl transfer. The C-terminal domain contains the regions of highest similarity to the phage RNAPs. Early in the evolution of eukaryotes there has been a switch from a multi-subunit prokaryotic polymerase to a single-subunit, phage-derived polymerase, encoded in the nuclear genome and imported into the mitochondria, to serve as the transcriptase of the mitochondrial genome. The POLRMT CTD is characteristic of the Pol I family of nucleic acid polymerases, typically described as resembling the shape of a cupped right hand, containing the fingers, palm and thumb subdomains. The palm subdomain contains several key structural motifs that are highly conserved among the different classes of nucleic acid polymerases | Homo sapiens |
| evolution | Rpo41 utilizes a promoter recognition loop to bind and recognize its promoter, analogous to the use of the specificity loop by T7 RNAP for this purpose | Saccharomyces cerevisiae |
| malfunction | at lower concentrations, pyrimidine nucleoside analogs have the potential to more easily inhibit mitochondrial transcription and mediate toxicity, given the ability to be readily phosphorylated and serve as efficient substrates for the enzyme | Homo sapiens |
| additional information | POLRMT distinct mechanisms for promoter recognition and transcription initiation, kinetic mechanism for POLRMT-catalyzed nucleotide incorporation, and structure-function relationship, nucleotidyl transfer and the nucleotide-addition cycle, detailed overview | Homo sapiens |
| physiological function | the enzyme is required for expression of 13 subunits of the respiratory chain complexes involved in oxidative phosphorylation and rRNAs and tRNAs, required for mitochondrial translation. Rpo41 can initiate transcription from negatively supercoiled templates and pre-melted promoter substrates in the absence of the yeast mitochondrial transcription factor, Mtf1. Mechanisms and species specificity for promoter recognition, overview | Saccharomyces cerevisiae |
| physiological function | the enzyme is required for expression of 13 subunits of the respiratory chain complexes involved in oxidative phosphorylation and two rRNAs and 22 tRNAs, required for mitochondrial translation. In addition to its role in transcription, in the mitochondria, POLRMT serves as the primase for mitochondrial DNA replication. Mechanisms and species specificity for promoter recognition, overview. Complex formation between the enzyme and the other transcription factors at the promoter, the structural elements of the enzyme are repositioned in such a way as to allow for specific promoter recognition, open complex formation and transcription initiation | Homo sapiens |
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