mRNA Editing (Homo sapiens)
From WikiPathways
Description
After transcription, some RNA molecules are altered to contain bases not encoded in the genome. Most often this involves the editing or modification of one base to another, but in some organisms can involve the insertion or deletion of a base. Such editing events alter the coding properties of mRNA.
RNA editing can be generally defined as the co- or post transcriptional modification of the primary sequence of RNA from that encoded in the genome through nucleotide deletion, insertion, or base modification mechanisms.
There are two pathways of RNA editing: the substitution/conversion pathway and the insertion/deletion pathway. The insertion/deletion editing occurs in protozoans like Trypanosoma, Leishmania; in slime molds like Physarum spp., and in some viral categories like paramyxoviruses, Ebola virus etc. To date, the substitution/conversion pathway has been observed in human along with other mammals, Drosophila, and some plants. The RNA editing processes are known to create diversity in proteins involved in various pathways like lipid transport, metabolism etc. and may act as potential targets for therapeutic intervention (Smith et al., 1997).
The reaction mechanisms of cytidine and adenosine deaminases is represented below. In both these reactions, NH3 is presumed to be released:
Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=75072
RNA editing can be generally defined as the co- or post transcriptional modification of the primary sequence of RNA from that encoded in the genome through nucleotide deletion, insertion, or base modification mechanisms.
There are two pathways of RNA editing: the substitution/conversion pathway and the insertion/deletion pathway. The insertion/deletion editing occurs in protozoans like Trypanosoma, Leishmania; in slime molds like Physarum spp., and in some viral categories like paramyxoviruses, Ebola virus etc. To date, the substitution/conversion pathway has been observed in human along with other mammals, Drosophila, and some plants. The RNA editing processes are known to create diversity in proteins involved in various pathways like lipid transport, metabolism etc. and may act as potential targets for therapeutic intervention (Smith et al., 1997).
The reaction mechanisms of cytidine and adenosine deaminases is represented below. In both these reactions, NH3 is presumed to be released:
Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=75072
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Ontology Terms
Saving...Bibliography
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- Hadjiagapiou C, Giannoni F, Funahashi T, Skarosi SF, Davidson NO.; ''Molecular cloning of a human small intestinal apolipoprotein B mRNA editing protein.''; PubMed Europe PMC Scholia
- Gerber AP, Keller W.; ''RNA editing by base deamination: more enzymes, more targets, new mysteries.''; PubMed Europe PMC Scholia
- Stuart K, Panigrahi AK.; ''RNA editing: complexity and complications.''; PubMed Europe PMC Scholia
- Henderson JO, Blanc V, Davidson NO.; ''Isolation, characterization and developmental regulation of the human apobec-1 complementation factor (ACF) gene.''; PubMed Europe PMC Scholia
- Gallo A, Keegan LP, Ring GM, O'Connell MA.; ''An ADAR that edits transcripts encoding ion channel subunits functions as a dimer.''; PubMed Europe PMC Scholia
- Zheng Y, Lorenzo C, Beal PA.; ''DNA editing in DNA/RNA hybrids by adenosine deaminases that act on RNA.''; PubMed Europe PMC Scholia
- Maris C, Masse J, Chester A, Navaratnam N, Allain FH.; ''NMR structure of the apoB mRNA stem-loop and its interaction with the C to U editing APOBEC1 complementary factor.''; PubMed Europe PMC Scholia
- Gerber A, O'Connell MA, Keller W.; ''Two forms of human double-stranded RNA-specific editase 1 (hRED1) generated by the insertion of an Alu cassette.''; PubMed Europe PMC Scholia
- Dawson TR, Sansam CL, Emeson RB.; ''Structure and sequence determinants required for the RNA editing of ADAR2 substrates.''; PubMed Europe PMC Scholia
- Gott JM, Emeson RB.; ''Functions and mechanisms of RNA editing.''; PubMed Europe PMC Scholia
- Cho DS, Yang W, Lee JT, Shiekhattar R, Murray JM, Nishikura K.; ''Requirement of dimerization for RNA editing activity of adenosine deaminases acting on RNA.''; PubMed Europe PMC Scholia
History
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External references
DataNodes
| View all... |
| Name | Type | Database reference | Comment |
|---|---|---|---|
| A to I edited RNA Editosome | Complex | REACT_3344 (Reactome)  | |
| A to I edited RNA Editosome | Complex | REACT_4604 (Reactome) | |
| A1CF | Protein | Q9NQ94 (Uniprot-TrEMBL) | |
| A1CF | Protein | Q9NQ94 (Uniprot-TrEMBL) | |
| ADAR | Protein | P55265 (Uniprot-TrEMBL) | |
| ADAR1 homodimer | Complex | REACT_4700 (Reactome) | |
| ADAR2 homodimer | Complex | REACT_3351 (Reactome) | |
| ADARB1 | Protein | P78563 (Uniprot-TrEMBL) | |
| ADARB1 | Protein | P78563 (Uniprot-TrEMBL) | |
| ADAR | Protein | P55265 (Uniprot-TrEMBL) | |
| APOBEC1 | Protein | P41238 (Uniprot-TrEMBL) | |
| C to U edited ApoB RNA Editosome complex | Complex | REACT_5264 (Reactome) | |
| Editosome | Complex | REACT_3053 (Reactome) | |
| Editosome | Complex | REACT_5072 (Reactome) | |
| Editosome for C to U editing | Complex | REACT_2389 (Reactome) | |
| H2O | Metabolite | CHEBI:15377 (ChEBI) | |
| NH3 | Metabolite | CHEBI:16134 (ChEBI) | |
| Stem-looped mRNA ACF complex | Complex | REACT_4484 (Reactome) | |
| Stem-looped mRNA | REACT_4094 (Reactome) | ||
| dsRNA duplex | REACT_4119 (Reactome) | ||
| mRNA with spliced exons | REACT_2708 (Reactome) | ||
| nascent pre-mRNA transcript | REACT_5393 (Reactome) |
Annotated Interactions
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| Source | Target | Type | Database reference | Comment |
|---|---|---|---|---|
| A to I edited RNA Editosome | Arrow | REACT_1105 (Reactome) | ||
| A to I edited RNA Editosome | Arrow | REACT_365 (Reactome) | ||
| A1CF | REACT_1850 (Reactome) | |||
| ADAR1 homodimer | REACT_1105 (Reactome) | |||
| ADAR1 homodimer | REACT_970 (Reactome) | |||
| ADAR2 homodimer | REACT_365 (Reactome) | |||
| ADAR2 homodimer | REACT_621 (Reactome) | |||
| APOBEC1 | REACT_869 (Reactome) | |||
| APOBEC1 | REACT_99 (Reactome) | |||
| C to U edited ApoB RNA Editosome complex | Arrow | REACT_869 (Reactome) | ||
| Editosome | REACT_1105 (Reactome) | |||
| Editosome | REACT_365 (Reactome) | |||
| Editosome for C to U editing | REACT_869 (Reactome) | |||
| H2O | REACT_1105 (Reactome) | |||
| H2O | REACT_365 (Reactome) | |||
| H2O | REACT_869 (Reactome) | |||
| NH3 | Arrow | REACT_1105 (Reactome) | ||
| NH3 | Arrow | REACT_365 (Reactome) | ||
| NH3 | Arrow | REACT_869 (Reactome) | ||
| REACT_1105 (Reactome) | At the beginning of this reaction, 1 molecule of 'Editosome (ADAR1) complex', and 1 molecule of 'H2O' are present. At the end of this reaction, 1 molecule of 'A to I edited RNA:Editosome (ADAR1) complex', and 1 molecule of 'NH3' are present. This reaction takes place in the 'nucleus' and is mediated by the 'double-stranded RNA adenosine deaminase activity' of 'ADAR1 homodimer '. | |||
| REACT_1276 (Reactome) | Site-specific A to I conversion requires dsRNA structures present around the editing site. These structures can be formed by exonic sequences and neighboring intronic sequences. An editing-site complementary sequence (ECS) has been identified in mice. Although minimal requirements for A to I editing have been identified, detailed mechanisms describing the individual steps are not yet well studied in humans. | |||
| REACT_1850 (Reactome) | A1CF protein is cytosolic in origin and is translocated to nucleus where it binds to the target RNA. The order of events in the formation of editosomes, namely, binding of A1CF and APOBEC-1 are not well elucidated in human cells. | |||
| REACT_186 (Reactome) | At the beginning of this reaction, 2 molecules of 'ADAR1 protein' is present. At the end of this reaction, 1 molecule of 'ADAR1 homodimer ' is present. This reaction takes place in the 'nucleus'. | |||
| REACT_208 (Reactome) | It is predicted that the target RNA could form secondary structures including stem-loop confirmation prior to the formation of editosome. | |||
| REACT_365 (Reactome) | At the beginning of this reaction, 1 molecule of 'H2O', and 1 molecule of 'Editosome (ADAR2) complex' are present. At the end of this reaction, 1 molecule of 'NH3', and 1 molecule of 'A to I edited RNA:Editosome (ADAR2) complex' are present. This reaction takes place in the 'nucleus' and is mediated by the 'double-stranded RNA adenosine deaminase activity' of 'ADAR2 homodimer'. | |||
| REACT_621 (Reactome) | At the beginning of this reaction, 1 molecule of 'dsRNA duplex', and 1 molecule of 'ADAR2 homodimer' are present. At the end of this reaction, 1 molecule of 'Editosome (ADAR2) complex' is present. This reaction takes place in the 'nucleus'. | |||
| REACT_869 (Reactome) | Hydrolytic deamination of cytidine leads to uridine. Ammonia is presumed to be released during this reaction. | |||
| REACT_970 (Reactome) | At the beginning of this reaction, 1 molecule of 'dsRNA duplex', and 1 molecule of 'ADAR1 homodimer ' are present. At the end of this reaction, 1 molecule of 'Editosome (ADAR1) complex' is present. This reaction takes place in the 'nucleus'. | |||
| REACT_990 (Reactome) | At the beginning of this reaction, 2 molecules of 'ADAR2 protein' is present. At the end of this reaction, 1 molecule of 'ADAR2 homodimer' is present. This reaction takes place in the 'nucleus'. | |||
| REACT_99 (Reactome) | APOBEC-1 binds to ACF:stem-looped mRNA complex forming the editosome. | |||
| Stem-looped mRNA ACF complex | REACT_99 (Reactome) | |||
| Stem-looped mRNA | REACT_1850 (Reactome) | |||
| dsRNA duplex | REACT_621 (Reactome) | |||
| dsRNA duplex | REACT_970 (Reactome) |
