Journal
NATURE CHEMICAL BIOLOGY
Volume 17, Issue 8, Pages 906-914Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41589-021-00817-3
Keywords
-
Categories
Funding
- National Institutes of Health [R01 GM102362, GM118178, GM128376]
- NASA Exobiology [NNX14AP59G]
- Synthorx, a Sanofi company
- Padma Harilela Endowment fund
- NASA [674509, NNX14AP59G] Funding Source: Federal RePORTER
Ask authors/readers for more resources
The study found that eukaryotic RNA polymerase II is capable of selectively recognizing unnatural base pairs with high fidelity, especially when the template strand contains dTPT3. Additionally, a novel 3'-RNA binding site termed the swing state was identified after rNaM addition. These results may pave the way for future studies in the design of transcription and translation strategies in higher organisms with expanded genetic codes.
The development of unnatural base pairs (UBPs) has greatly increased the information storage capacity of DNA, allowing for transcription of unnatural RNA by the heterologously expressed T7 RNA polymerase (RNAP) in Escherichia coli. However, little is known about how UBPs are transcribed by cellular RNA polymerases. Here, we investigated how synthetic unnatural nucleotides, NaM and TPT3, are recognized by eukaryotic RNA polymerase II (Pol II) and found that Pol II is able to selectively recognize UBPs with high fidelity when dTPT3 is in the template strand and rNaMTP acts as the nucleotide substrate. Our structural analysis and molecular dynamics simulation provide structural insights into transcriptional processing of UBPs in a stepwise manner. Intriguingly, we identified a novel 3 '-RNA binding site after rNaM addition, termed the swing state. These results may pave the way for future studies in the design of transcription and translation strategies in higher organisms with expanded genetic codes.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available