Table 3.
Intracellular proteins that bind PS ASOs
| Protein | Feature | ASO activity upon protein knockdown | ASO localization | Impact on ASO toxicity | ASO-protein co-localization |
|---|---|---|---|---|---|
| Nucleic acid binding proteins (33) | |||||
| Ago2* | RNA Binding | Reduced (free uptake) | Not characterized | Yes (P-bodies) | |
| CArG binding factor | RNA binding | Not characterized | Not characterized | ||
| DDX21 | RNA binding | Yes (toxic ASO) | |||
| DHX30 | RNA binding | No change | No change | ||
| EIF2S2 | RNA binding | Not characterized | Not characterized | ||
| eIF4H | RNA binding | No change | No change | ||
| GRSF | RNA binding | No change | No change | ||
| HMGB1 | DNA binding | No change | No change | No | |
| hnRNP D1Like | RNA binding | Not characterized | Not characterized | ||
| hnRNPA1$ | RNA binding | Not characterized | Not characterized | ||
| hnRNPA2 | RNA binding | Not characterized | Not characterized | ||
| hnRNPF | RNA binding | Not characterized | Not characterized | ||
| hnRNPH1 | RNA binding | Not characterized | Not characterized | ||
| hnRNPK | RNA binding | Increase | Yes | Yes | |
| hnRNPQ | RNA binding | No change | No change | ||
| hnRNPU | RNA binding | Not characterized | Not characterized | ||
| hnRNPUL | RNA binding | Not characterized | Not characterized | ||
| ILF2 | RNA binding | Not characterized | Not characterized | ||
| ILF3 | RNA binding | No change | No change | ||
| KHSRP | RNA binding | No change | No change | ||
| Ku70 | DNA binding | Increase | No change | No | |
| Ku80 | DNA binding | Increase | No change | No | |
| La/SSB | RNA binding | Reduce | Yes | No | |
| NCL# | RNA binding | No change | No change | Yes (toxic ASO) | |
| NPM1 | RNA binding | Reduce | Yes | Yes (toxic ASO) | |
| P54nrb | RNA/DNA binding | Increase | Yes | Yes | Yes |
| PC4/Sub1 | DNA binding | Reduce | No change | No | |
| PSF | RNA/DNA binding | Increase | Yes | Yes | Yes |
| PSPC1 | RNA binding | Increase | Yes | Yes | |
| RHA | RNA binding | No change | No change | ||
| RNase H1 | DNA/RNA duplex binding | Reduce | No change | Yes | |
| RNF163/ZNF9 | DNA binding | No change | No change | ||
| YBX1 protein | RNA binding | No change | Not characterized | ||
| Chaperone proteins (11) | |||||
| GRP78/Bip | Chaperone protein | No change | No change | ||
| HSC70 | Chaperone protein | Reduce | No change | No | |
| HSP90-AA1 | Chaperone protein | Reduce | No change | Yes | No |
| Hsp90-AB | Chaperone protein | Reduce | No change | Yes | |
| HSPA1L | Chaperone protein | Not characterized | Not characterized | ||
| TCP1-alpha | Chaperone protein | Reduce | Not characterized | Yes (LE) | |
| TCP1-beta | Chaperone protein | Reduce | Not characterized | Yes (PS-body, LE) | |
| TCP1-delta | Chaperone protein | Not characterized | Not characterized | Yes (LE) | |
| TCP1-episilon | Chaperone protein | Reduce | Not characterized | Yes (LE) | |
| TCP1-gamma | Chaperone protein | Not characterized | Not characterized | Yes (LE) | |
| TCP1-Theta | Chaperone protein | Not characterized | Not characterized | Yes (LE) | |
| Other proteins (17) | |||||
| ACLY | Enzyme | No change | No change | ||
| Albumin | Secreted | Not characterized | Not characterized | ||
| Annexin A2 | Membrane binding | Reduce | Yes | Yes (LE) | |
| ATAD3A | Membrane | No change | No change | ||
| FTCD/58K | Enzyme | Reduce | Yes | Yes (LE) | |
| IMP9 | Transport | Reduce | Yes | ||
| JKTPB1 delta 6 | hnNRP-like | Not characterized | Not characterized | ||
| KCTD12 | Membrane receptor | No change | No change | ||
| LRPPRC | Transport/transcription | No change | No change | ||
| NARS | tRNA synthase | No change | No change | ||
| NDKA | Enzyme | Not characterized | Not characterized | ||
| RAN | Transport | Reduce | Yes | ||
| SHMT2 | Enzyme | Not characterized | Not characterized | ||
| Thymidylate kinase | Enzyme | Not characterized | Not characterized | ||
| VARS | tRNA synthase | Reduce | No change | ||
| β-actin (ACTB) | Structure | Reduce | Not characterized | ||
| β-tubulin (TUBB2C) | Structure | No change | Not characterized | ||
Note: Bolded proteins demonstrated to influence ASO activity or localization.
Adapted from Crooke ST et al., Nat Biotechnology. 2017. 35:230–237.
*Castanotto D., et al., 2015, NAR.
# Weidner, D. A. et al., 1995, FEBS Lett.
$ Abdul-Manan et al., 1996, NAR.