ArticleProceedings of the National Academy of Sciences of the United States of America2014
Strand-specific (asymmetric) contribution of phosphodiester linkages on RNA polymerase II transcriptional efficiency and fidelity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Functional assays for transcription mechanisms in high-throughput.Methods (San Diego, Calif.) · 2019Review
- Dual coding potential of a 2',5'-branched ribonucleotide in DNA.RNA (New York, N.Y.) · 2019Article
- The mChemical science · 2017Article
- RNA polymerase II senses obstruction in the DNA minor groove via a conserved sensor motif.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Functional interplay between NTP leaving group and base pair recognition during RNA polymerase II nucleotide incorporation revealed by methylene substitution.Nucleic acids research · 2016Article
- Elucidation of the Dynamics of Transcription Elongation by RNA Polymerase II using Kinetic Network Models.Accounts of chemical research · 2016Article
- Impact of template backbone heterogeneity on RNA polymerase II transcription.Nucleic acids research · 2015Article
- RNA polymerase II transcriptional fidelity control and its functional interplay with DNA modifications.Critical reviews in biochemistry and molecular biology · 2015Review
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6 authors.
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Abstract
Nonenzymatic RNA polymerization in early life is likely to introduce backbone heterogeneity with a mixture of 2'-5' and 3'-5' linkages. On the other hand, modern nucleic acids are dominantly composed of 3'-5' linkages. RNA polymerase II (pol II) is a key modern enzyme responsible for synthesizing 3'-5'-linked RNA with high fidelity. It is not clear how modern enzymes, such as pol II, selectively recognize 3'-5' linkages over 2'-5' linkages of nucleic acids. In this work, we systematically investigated how phosphodiester linkages of nucleic acids govern pol II transcriptional efficiency and fidelity. Through dissecting the impacts of 2'-5' linkage mutants in the pol II catalytic site, we revealed that the presence of 2'-5' linkage in RNA primer only modestly reduces pol II transcriptional efficiency without affecting pol II transcriptional fidelity. In sharp contrast, the presence of 2'-5' linkage in DNA template leads to dramatic decreases in both transcriptional efficiency and fidelity. These distinct effects reveal that pol II has an asymmetric (strand-specific) recognition of phosphodiester linkage. Our results provided important insights into pol II transcriptional fidelity, suggesting essential contributions of phosphodiester linkage to pol II transcription. Finally, our results also provided important understanding on the molecular basis of nucleic acid recognition and genetic information transfer during molecular evolution. We suggest that the asymmetric recognition of phosphodiester linkage by modern nucleic acid enzymes likely stems from the distinct evolutionary pressures of template and primer strand in genetic information transfer during molecular evolution.
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