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RNA catalysis through compartmentalization

Nature Chemistry volume 4, pages 941–946 (2012)Cite this article

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Abstract

RNA performs important cellular functions in contemporary life forms. Its ability to act both as a catalyst and a storage mechanism for genetic information is also an important part of the RNA world hypothesis. Compartmentalization within modern cells allows the local concentration of RNA to be controlled and it has been suggested that this was also important in early life forms. Here, we mimic intracellular compartmentalization and macromolecular crowding by partitioning RNA in an aqueous two-phase system (ATPS). We show that the concentration of RNA is enriched by up to 3,000-fold in the dextran-rich phase of a polyethylene glycol/dextran ATPS and demonstrate that this can lead to approximately 70-fold increase in the rate of ribozyme cleavage. This rate enhancement can be tuned by the relative volumes of the two phases in the ATPS. Our observations support the importance of compartmentalization in the attainment of function in an RNA World as well as in modern biology.

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Figure 1: Hammerhead ribozyme and its rate acceleration through compartmentalization.
Figure 2: Length dependence of RNA partitioning.
Figure 3: Kinetics for hammerhead ribozymes in the kcat/KM regime.
Figure 4: Kinetics for HHL in ATPS with varying phase volume ratios.

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Acknowledgements

This work was supported by the National Science Foundation (grant CHE-0750196), co-funded by the MCB division. The authors thank members of the Bevilacqua and Keating laboratories for helpful comments on the manuscript. The authors also thank D. Dewey and M. Andes-Koback for help with fluorescence microscopy.

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Author notes

  1. Rosalynn C. Molden

    Present address: Present Address: Department of Chemistry, Princeton University, Princeton, New Jersey 08544, USA,

Authors and Affiliations

  1. Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania, 16802, USA

    Christopher A. Strulson, Rosalynn C. Molden, Christine D. Keating & Philip C. Bevilacqua

  2. Center for RNA Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, 16802, USA

    Christopher A. Strulson & Philip C. Bevilacqua

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Contributions

C.A.S. and R.C.M. performed the experiments. All authors contributed ideas, discussed the results, and wrote the manuscript.

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Correspondence to Christine D. Keating or Philip C. Bevilacqua.

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Strulson, C., Molden, R., Keating, C. et al. RNA catalysis through compartmentalization. Nature Chem 4, 941–946 (2012). https://doi.org/10.1038/nchem.1466

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