Albany 2013: Book of Abstracts
June 11-15 2013
©Adenine Press (2012)
Why G? Aggregation and Gelation of GMP with XMP: The Plot Thickens
GMP alone among the individual ribonucleotides exhibits a reversible self-aggregation through hydrogen bonding to form tetrads that are the building blocks of higher-order structures. These “G-tetrads” can further associate through π-π stacking to form chiral, columnar aggregates and, at higher monomer concentrations, lyotropic liquid crystalline phases. This alternate pathway for GMP should compete with its incorporation into oligonucleotides, which is why it is difficult to synthesize or amplify highly G-rich RNA or DNA with good efficiency in the absence of nature’s proteins such as helicases that function to unwind the strands.
Given this competing pathway for GMP, we can ask if it came to be one of the four ribonucleotides in modern RNA in spite of, or because of, its unique properties. Our hypothesis is that the competition between reversible aggregation and covalent polymerization directed RNA toward sequences that were best suited to life on early earth. We find support in the observation that the same interactions that promote self-assembly of monomeric GMP also promote folding of G-rich RNA and DNA sequences to form inter- and intramolecular G-quadruplex structures. Such sequences are prevalent throughout the biological world and are thought to serve important functions related to genomic stability and gene regulation. G-quadruplex structures are also common motifs in aptamers, which are combinatorially derived DNA or RNA sequences that exhibit highly selective, high affinity binding to molecular and macromolecular targets.
An important consideration for GMP aggregation in a prebiotic RNA World scenario is the effect of other XMP on GMP self-assembly. In this talk we will focus on the properties of solutions containing mixtures of GMP with AMP, CMP and UMP. The results show that each nucleotide exerts a different influence on the self-assembly of GMP, raising interesting questions about scenarios on prebiotic Earth that would be consistent with abiotic RNA polymerization.
This research is supported by NASA NAI through the New York Center for Astrobiology at Rensselaer Polytechnic Institute (Grant NNA09DA80A).
Linda B. McGown
Department of Chemistry and Chemical Biology, New York Center For Astrobiology,
Rensselaer Polytechnic Institute, Troy, NY 12180