Organisms today employ multiple enzymes, proteins and RNA, to catalyze biochemical reactions that are essential for life. According to the RNA world model, DNA and proteins were absent when life originated. Life began with RNA, which passed on genetic information and catalyzed biochemical reactions.

In order for RNA to pass on genetic information, it must be able to copy itself and produce a complementary sequence of RNA. A few months ago, we covered a RNA enzyme that can replicate RNA sequences that are long enough to have biochemical functions.

In a recent issue of Nature Chemistry, chemists propose an explanation for the step between the formation of random, short RNA sequences and that of relatively large, catalytically active RNA enzymes. They propose that RNA replication is possible without the presence of any enzymes at all. Instead, it's possible to perform surface-assisted copying of immobilized RNA.

There has been evidence from past studies of the individual monomers of RNA (A, U, G, and C) that indicated they could come together to form long sequences on the surfaces of minerals. Research groups also have found that immobilizing strands of DNA helps DNA replication. So, Christopher Deck and his colleagues decided to apply immobilization on RNA replication.

This isn't just interesting chemistry; Deck's paper proposes scenarios where RNA strands could have become adsorbed and immobilized on surfaces billions of years ago. RNA monomers and short sequences could have washed across these surfaces over time, and could have undergone reactions with the immobilized RNA.

To test if their proposal is feasible, Deck's team immobilized RNA templates on beads coated with DNA with a complementary sequence (the DNA base pairs to part of the RNA and holds it in place). The researchers then added a primer, a short sequence of RNA that base pairs to form a short stretch of double-stranded RNA, which serves as the initiation point where new RNA monomers can be added, creating a longer RNA sequence.

The authors also added a mixture of activated RNA monomers (A, G, C, and U with methylimidazole, leaving groups that make it easier for the monomers to react and link together) and a "micro-helper" to the template and primer. The micro-helper is a three base long RNA sequence that loosely hybridizes to the RNA template a short distance from where the primer binds. It probably serves to hold the RNA template in a better position undergoing chemical reactions.

After 18 days, the majority of the primers were extended by two or three monomers, and the researchers found that some of the primers increased in length by four bases; that is, four monomers were added. Thus, they were able to extend the length of some of the RNA primers (eight bases long) to a total of 12 bases. The authors also had some incorrect extensions, where the additional four monomers were not complementary to the sequence of the template.

Adding four bases in 18 days may not seem like much. In truth, it isn’t impressive at all when compared to what current enzymes can do. However, any primitive RNA copying system active billions of years ago would not have been as sophisticated and efficient as modern methods of RNA replication, and it wouldn't have needed to act as quickly. All it may have needed to do is create a complex mix of RNAs from which a replicator could form.

With that said, there are still many unanswered questions. Most obviously, his team used chemically activated RNA monomers. Would it be chemically possible for such activated monomers to have been present in the harsh conditions present on Earth before the advent of life?

Nature Chemistry, 2011. DOI: 10.1038/NCHEM.1086 (About DOIs)

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