Transcriptional processing of an unnatural base pair by eukaryotic RNA polymerase II
| Autor: | Liang Xu, Ilona Christy Unarta, Ji Shin, Floyd E. Romesberg, Rebekah J Karadeema, Jenny Chong, Ramanarayanan Krishnamurthy, Wei Wang, Jun Xu, Xuhui Huang, Aaron W. Feldman, Dong Wang, Juntaek Oh |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Transcription
Genetic Base pair Unnatural base pairs RNA polymerase II Computational biology Molecular Dynamics Simulation Article 03 medical and health sciences chemistry.chemical_compound Transcription (biology) medicine T7 RNA polymerase structural biology Molecular Biology Base Pairing Polymerase 030304 developmental biology 0303 health sciences biology 030302 biochemistry & molecular biology RNA Eukaryota Cell Biology chemistry Coding strand biology.protein synthetic biology transcription DNA medicine.drug |
| Zdroj: | Nature chemical biology |
| ISSN: | 1552-4469 1552-4450 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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