1. Biochemistry and Chemical Biology
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Nonenzymatic copying of RNA templates containing all four letters is catalyzed by activated oligonucleotides

  1. Noam Prywes
  2. J Craig Blain
  3. Francesca Del Frate
  4. Jack W Szostak  Is a corresponding author
  1. Harvard University, United States
  2. Ra Pharmaceuticals, United States
  3. Howard Hughes Medical Institute, Massachusetts General Hospital, United States
Research Article
  • Cited 70
  • Views 2,817
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Cite this article as: eLife 2016;5:e17756 doi: 10.7554/eLife.17756

Abstract

The nonenzymatic replication of RNA is a potential transitional stage between the prebiotic chemistry of nucleotide synthesis and the canonical RNA world in which RNA enzymes (ribozymes) catalyze replication of the RNA genomes of primordial cells. However, the plausibility of nonenzymatic RNA replication is undercut by the lack of a protocell-compatible chemical system capable of copying RNA templates containing all four nucleotides. We show that short 5′-activated oligonucleotides act as catalysts that accelerate primer extension, and allow for the one-pot copying of mixed sequence RNA templates. The fidelity of the primer extension products resulting from the sequential addition of activated monomers, when catalyzed by activated oligomers, is sufficient to sustain a genome long enough to encode active ribozymes. Finally, by immobilizing the primer and template on a bead and adding individual monomers in sequence, we synthesize a significant part of an active hammerhead ribozyme, forging a link between nonenzymatic polymerization and the RNA world.

Article and author information

Author details

  1. Noam Prywes

    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. J Craig Blain

    Ra Pharmaceuticals, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Francesca Del Frate

    Department of Molecular Biology, Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jack W Szostak

    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States
    For correspondence
    szostak@molbio.mgh.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Timothy W Nilsen, Case Western Reserve University, United States

Publication history

  1. Received: May 12, 2016
  2. Accepted: June 27, 2016
  3. Accepted Manuscript published: June 28, 2016 (version 1)
  4. Version of Record published: July 25, 2016 (version 2)

Copyright

© 2016, Prywes et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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