Non-enzymatic RNA polymerization

Project I RNA: Monomer self-condensation in matrices formed by amphiphile-bilayers

Lipid-bilayers composed of phosphatidylcholines have been reported to promote the polymerization of RNA from 5ZNMP. However, the mechanism, as well as the exact environmental conditions that are conducive to an efficient reaction remain obscure.

  • Explore the mechanism of polymerization by using derivatives of 5ZNMP
  • Determination of the impact of the matrice formation process on RNA oligomers
  • Investigation of the effect of solutes, such as salts, present during formation of the bilayer matrice

Contact: Pierre-Alain Monnard

Monomer self-condensation in matrices formed by amphiphile-bilayers

However, amphiphiles as complex as phosphatidylcholines were very improbable on the early Earth. Thus, we want to explore the promotion of bilayers formed of single chain amphiphiles. These systems must be stable at low pH.

  • Investigation of single chain amphiphiles that are stable at low pH. In particular their chemical and physical properties
  • Investigation of the promotion activity of monomer self-condensation to form RNA oligomers

Contact: Pierre-Alain Monnard

Oligomer condensation reactions in the eutectic phase in water-ice

The environment is known to very efficient promote self-condensation of activated monomers into polymers up to 30 mers in length. Such a length is the minimal length envisioned by the RNA-world proponents to obtain RNA aptamers or enzymes (ribozymes). The reactions at that point have exhausted the initial monomer supply. The issue is

  • Whether the further addition of monomers or the reactivation of the polymers could lead to longer products
  • Whether a chemical activation of the polymeric products could lead to products length that would corresponds to those (50-75 mers) that have shown (SELEX selection processes) to possess catalytic activity

Contact: Pierre-Alain Monnard

Template-directed RNA replication

Non-enzymatic, template-directed polymerization is an essential information-transfer step to yield a replicating system that will permit RNA self-replication/amplification and molecular evolution over several template-directed polymerization cycles. Conditions for an optimal reaction (high efficiency of elongation and low error rates) will be explored with respect to the component properties. Since the conformation adopted by primer-template complex will affect the reaction, RNA-analog templates with conformationally restricted backbones will be investigated.

  • Can the replication of RNA biopolymers (template-directed polymerization) occur within these structured media?
  • Are the conditions conducive to the monomer condensation applicable to this related polymerization?
  • What are the constraints imposed by the presence of a template on the reaction and do they alter molecular recognition between templates and monomers?

Contact: Pierre-Alain Monnard