mRNA Editing (Homo sapiens)

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2, 31, 4ADAR1 homodimer ADAR1 homodimer A to I edited RNAEditosome Editosome A to I edited RNAEditosome cytosolADAR2 homodimer nucleoplasmC to U edited ApoB RNAEditosome complex Stem-looped mRNAACF complex ADAR2 homodimer Editosome for C to U editing ADAR1 homodimer ADAR2 homodimer Editosome ADAR A to I edited RNAEditosome C to U edited ApoB RNAEditosome complexH2OA to I edited RNAEditosome APOBEC1ADARB1 A1CF dsRNA duplexADARB1A1CF A1CFADAR Editosome ADARStem-looped mRNAA1CF mRNA with spliced exonsnascent pre-mRNA transcriptStem-looped mRNAACF complexAPOBEC1NH3APOBEC1ADAR2 homodimerH2OADAR ADAR1 homodimerH2OADARB1 ADARB1 Editosome Editosome for C to U editingNH3


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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:

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Bibliography

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  1. 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
  2. Gerber AP, Keller W.; ''RNA editing by base deamination: more enzymes, more targets, new mysteries.''; PubMed Europe PMC Scholia
  3. Stuart K, Panigrahi AK.; ''RNA editing: complexity and complications.''; PubMed Europe PMC Scholia
  4. Henderson JO, Blanc V, Davidson NO.; ''Isolation, characterization and developmental regulation of the human apobec-1 complementation factor (ACF) gene.''; PubMed Europe PMC Scholia
  5. 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
  6. Zheng Y, Lorenzo C, Beal PA.; ''DNA editing in DNA/RNA hybrids by adenosine deaminases that act on RNA.''; PubMed Europe PMC Scholia
  7. 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
  8. 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
  9. Dawson TR, Sansam CL, Emeson RB.; ''Structure and sequence determinants required for the RNA editing of ADAR2 substrates.''; PubMed Europe PMC Scholia
  10. Gott JM, Emeson RB.; ''Functions and mechanisms of RNA editing.''; PubMed Europe PMC Scholia
  11. 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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CompareRevisionActionTimeUserComment
114672view16:14, 25 January 2021ReactomeTeamReactome version 75
113119view11:18, 2 November 2020ReactomeTeamReactome version 74
112353view15:28, 9 October 2020ReactomeTeamReactome version 73
101254view11:14, 1 November 2018ReactomeTeamreactome version 66
100793view20:42, 31 October 2018ReactomeTeamreactome version 65
100335view19:19, 31 October 2018ReactomeTeamreactome version 64
99880view16:02, 31 October 2018ReactomeTeamreactome version 63
99437view14:37, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93825view13:39, 16 August 2017ReactomeTeamreactome version 61
93375view11:21, 9 August 2017ReactomeTeamreactome version 61
86460view09:18, 11 July 2016ReactomeTeamreactome version 56
83416view11:10, 18 November 2015ReactomeTeamVersion54
81615view13:09, 21 August 2015ReactomeTeamVersion53
77075view08:37, 17 July 2014ReactomeTeamFixed remaining interactions
76780view12:14, 16 July 2014ReactomeTeamFixed remaining interactions
76103view10:16, 11 June 2014ReactomeTeamRe-fixing comment source
75815view11:36, 10 June 2014ReactomeTeamReactome 48 Update
75165view14:11, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74812view08:54, 30 April 2014ReactomeTeamReactome46
69042view17:53, 8 July 2013MaintBotUpdated to 2013 gpml schema
44922view10:47, 6 October 2011MartijnVanIerselOntology Term : 'transcription pathway' added !
42080view21:55, 4 March 2011MaintBotAutomatic update
39888view05:55, 21 January 2011MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
A to I edited RNA Editosome ComplexREACT_3344 (Reactome)
A to I edited RNA Editosome ComplexREACT_4604 (Reactome)
A1CF ProteinQ9NQ94 (Uniprot-TrEMBL)
A1CFProteinQ9NQ94 (Uniprot-TrEMBL)
ADAR ProteinP55265 (Uniprot-TrEMBL)
ADAR1 homodimerComplexREACT_4700 (Reactome)
ADAR2 homodimerComplexREACT_3351 (Reactome)
ADARB1 ProteinP78563 (Uniprot-TrEMBL)
ADARB1ProteinP78563 (Uniprot-TrEMBL)
ADARProteinP55265 (Uniprot-TrEMBL)
APOBEC1ProteinP41238 (Uniprot-TrEMBL)
C to U edited ApoB RNA Editosome complexComplexREACT_5264 (Reactome)
Editosome ComplexREACT_3053 (Reactome)
Editosome ComplexREACT_5072 (Reactome)
Editosome for C to U editingComplexREACT_2389 (Reactome)
H2OMetaboliteCHEBI:15377 (ChEBI)
NH3MetaboliteCHEBI:16134 (ChEBI)
Stem-looped mRNA ACF complexComplexREACT_4484 (Reactome)
Stem-looped mRNAREACT_4094 (Reactome)
dsRNA duplexREACT_4119 (Reactome)
mRNA with spliced exonsREACT_2708 (Reactome)
nascent pre-mRNA transcriptREACT_5393 (Reactome)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
A to I edited RNA Editosome ArrowREACT_1105 (Reactome)
A to I edited RNA Editosome ArrowREACT_365 (Reactome)
A1CFREACT_1850 (Reactome)
ADAR1 homodimerREACT_970 (Reactome)
ADAR1 homodimermim-catalysisREACT_1105 (Reactome)
ADAR2 homodimerREACT_621 (Reactome)
ADAR2 homodimermim-catalysisREACT_365 (Reactome)
APOBEC1REACT_99 (Reactome)
APOBEC1mim-catalysisREACT_869 (Reactome)
C to U edited ApoB RNA Editosome complexArrowREACT_869 (Reactome)
Editosome REACT_1105 (Reactome)
Editosome REACT_365 (Reactome)
Editosome for C to U editingREACT_869 (Reactome)
H2OREACT_1105 (Reactome)
H2OREACT_365 (Reactome)
H2OREACT_869 (Reactome)
NH3ArrowREACT_1105 (Reactome)
NH3ArrowREACT_365 (Reactome)
NH3ArrowREACT_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 complexREACT_99 (Reactome)
Stem-looped mRNAREACT_1850 (Reactome)
dsRNA duplexREACT_621 (Reactome)
dsRNA duplexREACT_970 (Reactome)
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