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Former results

Beyond the 4 canonical bases, over 100 modified nucleotides have been identified on transfer RNAs and ribosomal RNAs. Several authors have proposed that modified nucleotides are relics of an ancient RNA world that was more diversified and more heterogenous than the contemporary world. The ancestor of nucleic acids (IDA : Initial Darwinian Ancestor) probably did not present a uniform structure and was possibly the result of co-polymerisation of different families.

In our search for such primitive building blocks, we noticed that N6-ribosyl -adenine, a compound easily synthesized under prebiotic conditions (Fuller, W.D., Sanchez, R.A and Orgel, L.E, 1972) has a free imidazole, a chemically reactive group, and is therefore a potential analog of the amino acid, histidine. We synthesized this compound and showed that it was indeed as active as histidine in the hydrolysis of paranitrophenyl acetate, a model substrate often used in studying enzymes catalyzing esterase-type reactions (Maurel and Ninio, 1987 ; Maurel and Convert, 1990, Maurel, 1991). Furthermore, numerous studies have shown that compounds such as N6 or N3-ribosyl-purine could have been essential links between the protein and the RNA worlds (Maurel, 1992).

It is also interesting to notice that some of the purine bases of nucleic acids were identified in the Murchison meteorite (Stoks and Schwartz, 1981 ; Callahan et al, 2011).

Pursuing this line of investigation we showed that nucleic acid-like polymers such as poly(allylamine)s incorporating N6-substituted adenine rings exhibit pronounced catalytic activities in the hydrolysis of PNPesters (Maurel et Décout, 1992, 1995 a and b ; Décout et Maurel, 1993). A coupled experimental and theoretical study allowed us to speculate on the origin of kinetic co-operativity in prebiotic catalysts (Ricard, Vergne, Décout et Maurel, 1996 ; Maurel et Ricard, 2006).

We have selected, using the SELEX (Systematic Evolution of Ligand by EXponential enrichment) method, RNA aptamers for adenine. Analysis of the affinity of the RNA aptamer for other purines reveals a mode of purine recognition involving weak hydrophobic stacking interactions with the entire purine ring and additional hydrogen bonding with the 6-NH2 group of adenine (Meli, Vergne, Décout et Maurel, 2002). Adenine and adenylated compounds play key roles in contemporary metabolisms and evidences exist that they played an important role in early evolution (Maurel et Décout, 1999 ; Meli, Albert-Fournier, Maurel, 2001). Cofactor assisted ribozymes could be considered as remnants of RNA world ribozymes handling exogenous prebiotic reactive ligands. RNAs binding specific cofactors, amino acids or analogs may have provided a kind of scaffold modeling early relationships between primeval tRNAs and specific reactive groups. They would have been pre-adaptors that led to the emergence of the modern genetic apparatus.
We discovered a hairpin ribozyme strictly dependent on adenine (ADHR) as external co-factor for the reversible self-cleavage reaction. This co-ribozyme acts as a ribozyme using adenine as cofactor to perform a ribonuclease-type activity (Meli et al, 2002 ; 2003).

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