Copying of Mixed-Sequence RNA Templates inside Model Protocells

Derek K. O'Flaherty, Neha P. Kamat, Fatima N. Mirza, Li Li, Noam Prywes*, Jack W. Szostak

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


The chemical replication of RNA inside fatty acid vesicles is a plausible step in the emergence of cellular life. On the primitive Earth, simple protocells with the ability to import nucleotides and short oligomers from their environment could potentially have replicated and retained larger genomic RNA oligonucleotides within a spatially defined compartment. We have previously shown that short 5′-phosphoroimidazolide-activated "helper" RNA oligomers enable the nonenzymatic copying of mixed-sequence templates in solution, using 5′-phosphoroimidazolide-activated mononucleotides. Here, we report that citrate-chelated Mg2+, a catalyst of nonenzymatic primer extension, enhances fatty acid membrane permeability to such short RNA oligomers up to the size of tetramers, without disrupting vesicle membranes. In addition, selective permeability of short, but not long, oligomers can be further enhanced by elevating the temperature. The ability to increase the permeability of fatty acid membranes to short oligonucleotides allows for the nonenzymatic copying of RNA templates containing all four nucleotides inside vesicles, bringing us one step closer to the goal of building a protocell capable of Darwinian evolution.

Original languageEnglish (US)
Pages (from-to)5171-5178
Number of pages8
JournalJournal of the American Chemical Society
Issue number15
StatePublished - Apr 18 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry
  • Catalysis
  • Colloid and Surface Chemistry


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