Albany 2013: Book of Abstracts
June 11-15 2013
©Adenine Press (2012)
Efficient and High-Fidelity Copying of an RNA-like Model Prebiotic System
Non-enzymatic RNA replication would provide an important bridge to the RNA world. However, the demonstration of efficient and high-fidelity copying chemistry remains a great experimental challenge. It requires an efficient mechanism that can lead to both a high rate of polymerization and a high degree of fidelity in the copying chemistry. Previous experiments concerning non-enzymatic template-directed syn-thesis of RNA with activated monomers have led to the copying of short RNA templates, but these reac-tions are generally slow (taking days to weeks) and highly error-prone. Therefore, the ability to efficiently and accurately copy arbitrary template sequences remains frustratingly out of reach. N3′-P5′-linked phos-phoramidate DNA is a highly reactive model for self-replicating genetic materials and has been used for studies of non-enzymatic RNA self-replication. It is also an excellent RNA mimic, due to its similar over-all duplex structure, rigidity, and level of hydration (Tereshko, Gryaznov & Egli, 1998). Our experiments show that the high reactivity imparted by the presence of an amino nucleophile allows rapid and efficient copying of all four nucleobases on both homopolymeric and mixed templates. On the other hand, G:T wobble pairing leads to a high error rate. We have therefore investigated the use of the modified nu-cleobase, 2-thio T (Ts) (Sintim & Kool, 2006), to suppress formation of the G:T wobble base-pair.
H. O. Sintim, & E. T. Kool. (2006) Enhanced Base Pairing and Replication Efficiency of Thio-thymidines, Expanded-size Variants of Thymidine. J. Am. Chem. Soc., 128, 396-397.
1Howard Hughes Medical Institute