Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytoplasm | - |
Homo sapiens | 5737 | - |
nucleus | - |
Homo sapiens | 5634 | - |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | Homo sapiens | RNaseH1-dependent antisense oligonucleotides (ASOs) activity in human cells, mechanism and regulation, overview | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | O60930 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
A-431 cell | - |
Homo sapiens | - |
HEK-293 cell | - |
Homo sapiens | - |
HeLa cell | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | RNaseH1-dependent antisense oligonucleotides (ASOs) activity in human cells, mechanism and regulation, overview | Homo sapiens | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
RNase H1 | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
physiological function | RNase H1-dependent antisense oligonucleotides (ASOs) can recruit RNase H1 to cleave the RNA substrate within the region complementary to the DNA portion of ASOs. ASOs can degrade complementary RNAs in both the nucleus and the cytoplasm. Since cytoplasmic mRNAs are actively engaged in translation, ASO activity may thus be affected by translating ribosomes that scan the mRNAs. mRNAs associated with ribosomes can be cleaved using ASOs and that translation can alter ASO activity. Translation inhibition tends to increase ASO activity when targeting the coding regions of efficiently translated mRNAs, but not nuclear non-coding RNAs or less efficiently translated mRNAs. Increasing the level of RNase H1 protein eliminates the enhancing effects of translation inhibition on ASO activity, suggesting that RNase H1 recruitment to ASO/mRNA heteroduplexes is a rate limiting step and that translating ribosomes can inhibit RNase H1 recruitment. Consistently, ASO activity is not increased by translation inhibition when targeting the 3' UTRs, independent of the translation efficiency of the mRNAs. Contrarily, the activity of 3' UTR-targeting ASOs tends to be reduced upon translation inhibition, likely due to decreased accessibility. Overexpression of RNaseH1 attenuates the enhancement in ASO activity by CHX treatment | Homo sapiens |