Pathways of nucleic acid metabolism and innate immune sensing (WP4705)
Homo sapiens
Cytosolic DNA and RNA can lead to innate immune sensing via three paths. DNA is sensed by cGAS, which activates STING. RNA is sensed by MDA5 and RIG-I, which activates MAVS. An activation of STING or MAVS lead to phosphorylation of IFR3, which triggers innate immune responses. This pathway was inspired by Chapter 14 of the 5th edition of the book of Blau (in press).
Authors
Denise Slenter , Laurent Winckers , Egon Willighagen , and Eric WeitzActivity
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Organisms
Homo sapiensCommunities
Inherited Metabolic Disorders (IMD) PathwaysAnnotations
Pathway Ontology
signaling pathway in the innate immune response altered DNA repair pathway| Label | Type | Compact URI | Comment |
|---|---|---|---|
| dNTP pools | Metabolite | chebi:61560 | |
| Adenosine | Metabolite | chebi:74411 | |
| dN | Metabolite | chebi:18274 | |
| Inosine | Metabolite | chebi:82852 | |
| IFIH1 | GeneProduct | ensembl:ENSG00000115267 | |
| DDX58 | GeneProduct | ensembl:ENSG00000107201 | |
| IFNB | GeneProduct | ensembl:ENSG00000171855 | |
| TMEM173 | GeneProduct | ensembl:ENSG00000184584 | cGAS which signals via STING (encoded by TMEM173) |
| RNase T2 | Protein | uniprot:O00584 | |
| SAMHD1 | Protein | uniprot:Q9Y3Z3 | |
| STING | Protein | uniprot:Q86WV6 | |
| RNase H2subunit A | Protein | uniprot:O75792 | Catalytic subunit |
| TREX1 | Protein | uniprot:Q9NSU2 | Cytosolic deoxyribonuclease anchored in the outer nuclear membrane. A lack of TREX1 causes DNA accumulation, both within the nucleus and the cytosol. |
| OAS1 | Protein | uniprot:P00973 | |
| RNase L | Protein | uniprot:Q05823 | |
| ADAR | Protein | uniprot:P55265 | Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing |
| cGAS | Protein | uniprot:Q8N884 | DNA sensor |
| MAVS | Protein | uniprot:Q7Z434 | mitochondrial antiviral signaling (MAVS) |
| IRF3 | Protein | uniprot:Q14653 | |
| MDA5 | Protein | uniprot:Q9BYX4 | Cytosolic RNA sensorActivating mutations in RIG-I and MDA5 increase receptor affinity resulting in constitutive type I IFN signaling. |
| RIG-I | Protein | uniprot:O95786 | cytosolic RNA sensorActivating mutations in RIG-I and MDA5 increase receptor affinity resulting in constitutive type I IFN signaling. |
| RNase H2subunit B | Protein | uniprot:Q5TBB1 | Noncatalytic subunit |
| RNase H2subunit C | Protein | uniprot:Q8TDP1 | Noncatalytic subunit |
| SAMHD1 | Protein | uniprot:Q9Y3Z3 | SAMHD1 has also ribonuclease activity, suggesting that a loss of SAMHD1 may lead to RNA accumulation. |
| IRF3 | Protein | uniprot:Q14653 | |
| ISGs | Protein | interpro:IPR000471 | interferon-responsive genes |
References
- Expression and regulation by interferon of a double-stranded-RNA-specific adenosine deaminase from human cells: evidence for two forms of the deaminase. Patterson JB, Samuel CE. Mol Cell Biol. 1995 Oct;15(10):5376–88. PubMed Europe PMC Scholia
- Mammalian retroelements. Deininger PL, Batzer MA. Genome Res. 2002 Oct;12(10):1455–65. PubMed Europe PMC Scholia
- Requirement of dimerization for RNA editing activity of adenosine deaminases acting on RNA. Cho DSC, Yang W, Lee JT, Shiekhattar R, Murray JM, Nishikura K. J Biol Chem. 2003 May 9;278(19):17093–102. PubMed Europe PMC Scholia