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Researchers find a missing component in effort to create primitive, synthetic cells
Date:11/28/2013

drive nonenzymatic replication of RNA, which many scientists believe was the first nucleic acid to develop.

To address the incompatibility between the need for Mg2+ to drive assembly of the RNA molecule and the ion's ability to degrade fatty acid membranes, they tested several chelators small molecules that bind tightly to metal ions for their ability to protect fatty acid vesicles from the potentially destabilizing effects of Mg2+. Citrate and several other chelators were found to be effective in protecting the membranes of fatty acid vesicles from disruption.

To test whether the presence of the tested chelators would allow Mg2+-catalyzed RNA assembly, the investigators placed molecules consisting of short primer RNA strands bound to longer RNA templates into fatty acid vesicles. The unbound, single-strand portion of the template consisted of a sequence of cytosine (C) nucleotides. In the presence of Mg2+ and one of four chelating molecules, one of which was citrate, the researchers then added activated G, the nucleotide that base-pairs with C in nucleic acids.

The desired reaction diffusion of G nucleotides through the vesicle membrane to complete a double-stranded RNA molecule by binding to the C nucleotides of the template proceeded fastest in the presence of citrate. In fact two of the other tested chelators completely prevented extension of the RNA primer.

"While other molecules can protect membranes against the magnesium ion," Szostak explains, "they don't let RNA chemistry go on. We think that citrate is able both to protect membranes and to allow RNA copying to proceed by covering only one face to the magnesium ion, protecting the membrane while allowing RNA chemistry to work." He and Adamala also found that continually refreshing the activated guanine nucleotide solution by flushing out broken down molecules and adding fresh nucleotides improved the efficiency of RNA replication.

Szostak notes
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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
Source:Eurekalert

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