A Chemical Perspective on Transcriptional Fidelity: Dominant Contributions of Sugar Integrity Revealed by Unlocked Nucleic Acids

Authors

  • Dr. Liang Xu,

    1. Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of California, San Diego, La Jolla, CA 92093-0625 (USA)
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    • These authors contributed equally to this work.

  • Steven W. Plouffe,

    1. Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of California, San Diego, La Jolla, CA 92093-0625 (USA)
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    • These authors contributed equally to this work.

  • Jenny Chong,

    1. Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of California, San Diego, La Jolla, CA 92093-0625 (USA)
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  • Prof. Dr. Jesper Wengel,

    1. Nucleic Acid Center and Biomolecular Nanoscale Engineering Center, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense M (Denmark)
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  • Prof. Dr. Dong Wang

    Corresponding author
    1. Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of California, San Diego, La Jolla, CA 92093-0625 (USA)
    • Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of California, San Diego, La Jolla, CA 92093-0625 (USA)

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  • D.W. acknowledges the NIH (GM102362, Kimmel Scholar Award from the Sidney Kimmel Foundation for Cancer Research, and start-up funds from Skaggs School of Pharmacy and Pharmaceutical Sciences, UCSD. S.W.P. was supported in part by the UCSD Graduate Training Program in Cellular and Molecular Pharmacology training grant (T32 GM007752). We thank Dr. E. Peter Geiduschek, Dr. Eric T. Kool, and Dr. Yitzhak Tor for their critical reading of our manuscript.

Abstract

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Transcription unlocked: A synthetic chemical biology approach involving unlocked nucleic acids was used to dissect the contribution of sugar backbone integrity to the RNA Polymerase II (Pol II) transcription process. An unexpected dominant role for sugar-ring integrity in Pol II transcriptional efficiency and fidelity was revealed.

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