Cellular sensors and responders to foreign RNA and DNA
Reagents of RNAi and miRNA technologies delivered to cells either by transfection or released from expression vectors may be recognized by specific cellular sensors of foreign RNA and DNA. After the activation of cytoplasmic (RIG-I, MDA5, PKR, and OAS1-3) and endosomal (TLR3, 7, and 8) sensors, a signal is transduced through specific adaptor proteins to transcription factors which in turn stimulate production of proinflammatory cytokines and IFN. The activation of other sensors may induce cell death by pyroptosis (AIM2, NLRP3). TLR3 localization (denoted by asterisk) is cell type dependent. Endosomal TLRs are expressed mainly in the immune system cells.
| Sensor symbol |
Localization | Ligand | Pathway | PKR | cytoplasm, nucleus | dsRNA, 5-prime-triphosphate RNA | BIOCARTA |
|---|---|---|---|
| OAS1 | cytoplasm, nucleus, membranes | dsRNA | RNAimmuno |
| OAS2 | cytoplasm, nucleus, membranes | dsRNA | RNAimmuno |
| OAS3 | microsomes | dsRNA | RNAimmuno |
| RIG-I | cytoplasm | blunt-ended dsRNA, 5-prime-triphosphate RNA | KEGG_1 KEGG_2 InvivoGen |
| MDA5 | cytoplasm | long dsRNA | KEGG InvivoGen |
| TLR3 | endosome, cell membrane, endoplasmic reticulum membrane | dsRNA | KEGG BIOCARTA InvivoGen |
| TLR7 | endosomes, membranes | ssRNA | KEGG BIOCARTA InvivoGen |
| TLR8 | endosomes, membranes | ssRNA | KEGG BIOCARTA InvivoGen |
| TLR9 | endosomes, membranes | CpG DNA | KEGG BIOCARTA InvivoGen |
| NLRP3 | cytoplasm | RNA | KEGG |
| NOD2 | cytoplasm | ssRNA | KEGG RNAimmuno |
| AIM2 | cytoplasm | DNA | KEGG |
| ZBP1 | cytoplasm | DNA | KEGG |