Did Life Begin with “RNA on Steroids”?

The “RNA world” hypothesis posits that life, and biological evolution, began with self-replicating RNA molecules. Before DNA, before protein enzymes, RNA molecules both stored hereditary information, and performed the catalytic functions required for replication. All cells today still depend on RNA catalysis for some core functions such as protein synthesis by the ribosomes, where the ribosomal RNA molecule forms the peptidyl transferase catalytic center, rather than any of the ribosomal proteins. Other enzymatic RNAs (ribozymes) catalyze self-splicing, RNA cleavage, RNA ligation, and RNA polymerase activities.

All reactions involving ribozymes require divalent cations, preferably Mg2+. Recent and ongoing research by the laboratories of Loren Williams, Nick Hud, Roger Wartell, and Stephen Harvey at Georgia Tech asked whether Fe2+ could substitute for Mg2+ in RNA folding and catalysis (Athavale et al. 2012). Fe2+ is a soluble form of iron that was abundant in the Earth’s early oceans until cyanobacterial ancestors began to produce large quantities of molecular oxygen (O2), around 2.7 billion years go. In the presence of O2, Fe2+ is oxidized to Fe3+, which is insoluble and precipitates in the form of iron oxide (rust). This massive precipitation of iron oxide onto ocean sediments formed banded iron formations that can be found around the world.

Athavale et al. discovered that Fe2+, with coordination geometry similar to Mg2+, could indeed substitute for Mg2+ in folding and catalysis by ribozymes. Moreover, Fe2+ enhanced ligation by the Tetrahymena Group I intron by 25-fold and cleavage by a hammerhead ribozyme by 3-fold compared to equivalent concentrations of Mg2+.

Athavale et al. 2012 Fig. 3 Ribozyme activity is enhanced by Fe2+ compared to Mg2+.
A) L1 ribozyme ligase activity is enhanced in Fe2+ compared to Mg2+. Reaction progress was monitored by gel electrophoresis. B) Hammerhead ribozyme activity is enhanced in Fe2+ compared to Mg2+. Reactions were monitored by both gel electrophoresis and capillary electrophoresis, which gave similar results.

These results help address one of the criticisms of the RNA world hypothesis, that RNA catalysis is slow and inefficient. In the anoxic oceans of the Archaean eon (from the origin of life to circa 2.5 billion years ago), dissolved Fe2+ would have greatly enhanced the catalytic activities of RNA molecules. In the words of Loren Williams, RNA in the presence of Fe2+ was like “RNA on steroids” (H Thompson 2012).


Athavale SS, AS Petrov, C Hsiao, D Watkins, CD Prickett, JJ Gossett, L Lie, JC Bowman, E O’Neill, CR Bernier, NV Hud, RM Wartell, SC Harvey, LD Williams, 2012. RNA folding and catalysis mediated by Iron (II), PLoS ONE 7(5): e38024. doi:10.1371/journal.pone.0038024

H Thompson 2012, Dissolved iron may have been key to RNA-based life, Nature News Blog http://blogs.nature.com/news/2012/06/dissolved-iron-may-have-been-key-to-rna-based-life.html


About jchoigt

I'm an Associate Professor in the School of Biology at Georgia Tech, and Faculty Coordinator of the Professional MS Bioinformatics degree program.
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