한빛사논문
- 조회1,138
Juntaek Oh1, Ji Shin1,7,10, Ilona Christy Unarta2,10, Wei Wang1,8, Aaron W. Feldman3, Rebekah J. Karadeema 3, Liang Xu1,9, Jun Xu1, Jenny Chong1, Ramanarayanan Krishnamurthy 3, Xuhui Huang 2, Floyd E. Romesberg4 and Dong Wang1,5,6,*
1Division of Pharmaceutical Sciences, Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA. 2Department of Chemistry, The Hong Kong University of Science and Technology, Kowloon, Hong Kong. 3Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA. 4Synthorx, La Jolla, CA, USA. 5Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA. 6Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA. 7Present address: Department of Molecular Microbiology, Center for Advanced Laboratory Medicine, University of California, San Diego, La Jolla, CA, USA. 8Present address: Advanced Medical Research Institute, Shandong University, Jinan, China. 9Present address: Department of Chemistry, Sun Yat-Sen University, Guangzhou, China. 10These authors contributed equally: Ji Shin, Ilona Christy Unarta.
*Corresponding author
Abstract
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.
논문정보
- Research article
- 2021년 06월 (BRIC 등록일 2021-06-25)
- 국외 연구진
- 생명과학 > 구조생물 및 생물물리학
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