mRNA Editing (Homo sapiens)

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3, 11881, 51, 56852, 47, 1096cytosolnucleoplasmADARB1 A to I editedRNA:Editosome(ADAR2) complexAPOBEC3A ADAR1 homodimerStem-looped mRNAA1CF APOBEC2 APOBEC3B Editosome (ADAR1)complexADARB1 H2OEditosome (ADAR2)complexAPOBEC3C ADARdsRNA duplexAPOBEC1(1-236) A to I edited RNA dsRNA duplex NH3H2OAPOBEC4 APOBEC4 A1CFEditosome for C to UeditingADARB1 ADAR APOBEC2 APOBEC3H APOBEC1(1-236) APOBEC1(1-236) C to U edited ApoB RNA APOBEC3C ADAR2 homodimerA1CF nascent pre-mRNAtranscriptA to I edited RNA APOBEC3B H2OStem-looped mRNA mRNA with splicedexonsADAR dsRNA duplex C to U edited ApoBRNA:EditosomecomplexAPOBEC1(APOBEC2,3A,3B,3C,3H,4)APOBEC3A APOBEC2 A to I editedRNA:Editosome(ADAR1) complexAPOBEC3H APOBEC3B APOBEC3C Stem-looped mRNA:ACFcomplexAPOBEC4 ADAR APOBEC3H Stem-looped mRNA NH3A1CF APOBEC3A ADARB1


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:
View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 75072
Reactome-version 
Reactome version: 66
Reactome Author 
Reactome Author: Carmichael, Gordon G

Quality Tags

Ontology Terms

 

Bibliography

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  1. 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
  2. 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
  3. Stuart K, Panigrahi AK.; ''RNA editing: complexity and complications.''; PubMed Europe PMC
  4. Henderson JO, Blanc V, Davidson NO.; ''Isolation, characterization and developmental regulation of the human apobec-1 complementation factor (ACF) gene.''; PubMed Europe PMC
  5. 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
  6. Zheng Y, Lorenzo C, Beal PA.; ''DNA editing in DNA/RNA hybrids by adenosine deaminases that act on RNA.''; PubMed Europe PMC
  7. Dawson TR, Sansam CL, Emeson RB.; ''Structure and sequence determinants required for the RNA editing of ADAR2 substrates.''; PubMed Europe PMC
  8. 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
  9. 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
  10. Gerber AP, Keller W.; ''RNA editing by base deamination: more enzymes, more targets, new mysteries.''; PubMed Europe PMC
  11. Gott JM, Emeson RB.; ''Functions and mechanisms of RNA editing.''; PubMed Europe PMC

History

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CompareRevisionActionTimeUserComment
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

View all...
NameTypeDatabase referenceComment
A to I edited

RNA:Editosome

(ADAR1) complex
ComplexR-HSA-75089 (Reactome)
A to I edited

RNA:Editosome

(ADAR2) complex
ComplexR-HSA-77611 (Reactome)
A to I edited RNA R-ALL-75088 (Reactome)
A1CF ProteinQ9NQ94 (Uniprot-TrEMBL)
A1CFProteinQ9NQ94 (Uniprot-TrEMBL)
ADAR ProteinP55265 (Uniprot-TrEMBL)
ADAR1 homodimerComplexR-HSA-111236 (Reactome)
ADAR2 homodimerComplexR-HSA-111235 (Reactome)
ADARB1 ProteinP78563 (Uniprot-TrEMBL)
ADARB1ProteinP78563 (Uniprot-TrEMBL)
ADARProteinP55265 (Uniprot-TrEMBL)
APOBEC1(1-236) ProteinP41238 (Uniprot-TrEMBL)
APOBEC1(APOBEC2,3A,3B,3C,3H,4)ComplexR-HSA-8875002 (Reactome)
APOBEC2 ProteinQ9Y235 (Uniprot-TrEMBL)
APOBEC3A ProteinP31941 (Uniprot-TrEMBL)
APOBEC3B ProteinQ9UH17 (Uniprot-TrEMBL)
APOBEC3C ProteinQ9NRW3 (Uniprot-TrEMBL)
APOBEC3H ProteinQ6NTF7 (Uniprot-TrEMBL)
APOBEC4 ProteinQ8WW27 (Uniprot-TrEMBL)
C to U edited ApoB

RNA:Editosome

complex
ComplexR-HSA-83676 (Reactome)
C to U edited ApoB RNA R-ALL-75085 (Reactome)
Editosome (ADAR1) complexComplexR-HSA-75087 (Reactome)
Editosome (ADAR2) complexComplexR-HSA-77610 (Reactome)
Editosome for C to U editingComplexR-HSA-77606 (Reactome)
H2OMetaboliteCHEBI:15377 (ChEBI)
NH3MetaboliteCHEBI:16134 (ChEBI)
Stem-looped mRNA R-ALL-77601 (Reactome)
Stem-looped mRNA:ACF complexComplexR-HSA-77605 (Reactome)
Stem-looped mRNAR-ALL-77601 (Reactome)
dsRNA duplex R-ALL-75086 (Reactome)
dsRNA duplexR-ALL-75086 (Reactome)
mRNA with spliced exonsR-ALL-72156 (Reactome)
nascent pre-mRNA transcriptR-ALL-72084 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
A to I edited

RNA:Editosome

(ADAR1) complex
ArrowR-HSA-77614 (Reactome)
A to I edited

RNA:Editosome

(ADAR2) complex
ArrowR-HSA-77615 (Reactome)
A1CFR-HSA-77608 (Reactome)
ADAR1 homodimerArrowR-HSA-111237 (Reactome)
ADAR1 homodimerR-HSA-75090 (Reactome)
ADAR1 homodimermim-catalysisR-HSA-77614 (Reactome)
ADAR2 homodimerArrowR-HSA-111238 (Reactome)
ADAR2 homodimerR-HSA-77613 (Reactome)
ADAR2 homodimermim-catalysisR-HSA-77615 (Reactome)
ADARB1R-HSA-111238 (Reactome)
ADARR-HSA-111237 (Reactome)
APOBEC1(APOBEC2,3A,3B,3C,3H,4)R-HSA-77609 (Reactome)
APOBEC1(APOBEC2,3A,3B,3C,3H,4)mim-catalysisR-HSA-83677 (Reactome)
C to U edited ApoB

RNA:Editosome

complex
ArrowR-HSA-83677 (Reactome)
Editosome (ADAR1) complexArrowR-HSA-75090 (Reactome)
Editosome (ADAR1) complexR-HSA-77614 (Reactome)
Editosome (ADAR2) complexArrowR-HSA-77613 (Reactome)
Editosome (ADAR2) complexR-HSA-77615 (Reactome)
Editosome for C to U editingArrowR-HSA-77609 (Reactome)
Editosome for C to U editingR-HSA-83677 (Reactome)
H2OR-HSA-77614 (Reactome)
H2OR-HSA-77615 (Reactome)
H2OR-HSA-83677 (Reactome)
NH3ArrowR-HSA-77614 (Reactome)
NH3ArrowR-HSA-77615 (Reactome)
NH3ArrowR-HSA-83677 (Reactome)
R-HSA-111237 (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 (Cho et al.2003, Gallo et al. 2003).

This reaction takes place in the 'nucleus'.

R-HSA-111238 (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 (Cho et al.2003, Gallo et al. 2003).

This reaction takes place in the 'nucleus'.

R-HSA-75090 (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' (Cho et al. 2003).

R-HSA-77607 (Reactome) It is predicted that the target RNA could form secondary structures including stem-loop confirmation prior to the formation of editosome (Maris et al.2005).
R-HSA-77608 (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 (Maris et al.2005).
R-HSA-77609 (Reactome) APOBEC-1 binds to ACF:stem-looped mRNA complex forming the editosome (Maris et al.2005).
R-HSA-77612 (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 (Gerber e al.2001, Dawson et al.2004 ). Although minimal requirements for A to I editing have been identified, detailed mechanisms describing the individual steps are not yet well studied in humans.
R-HSA-77613 (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'.

R-HSA-77614 (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 ' (Zheng et al.2017).

R-HSA-77615 (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' (Zheng et al.2017).

R-HSA-83677 (Reactome) Hydrolytic deamination of cytidine leads to uridine. Ammonia is presumed to be released during this reaction.

Stem-looped mRNA:ACF complexArrowR-HSA-77608 (Reactome)
Stem-looped mRNA:ACF complexR-HSA-77609 (Reactome)
Stem-looped mRNAArrowR-HSA-77607 (Reactome)
Stem-looped mRNAR-HSA-77608 (Reactome)
dsRNA duplexArrowR-HSA-77612 (Reactome)
dsRNA duplexR-HSA-75090 (Reactome)
dsRNA duplexR-HSA-77613 (Reactome)
mRNA with spliced exonsR-HSA-77607 (Reactome)
nascent pre-mRNA transcriptR-HSA-77612 (Reactome)
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