According to the RNA World Hypothesis, RNA was a key molecule that was utilized by the earliest life on Earth to store genetic information and to catalyze chemical reactions.  This raises the question, however, of how RNA formed under prebiotic conditions on the early Earth.  In fact, the issue of the complete synthesis of RNA nucleotides has been a major stumbling block for the RNA World Hypothesis.  The sugar found in the backbone of both DNA and RNA, ribose, has been particularly problematic, as the most prebiotically plausible chemical reaction schemes have typically yielded only a small amount of ribose mixed with a diverse assortment of other sugar molecules.

These difficulties have led some scientists to hypothesize that RNA was preceded by other RNA-like molecules that were more stable and readily synthesized under prebiotic conditions. Based on analyses of meteorites, such as the Murchison meteorite, other scientists contest that some components of RNA may have formed in space and arrived on Earth rather than being formed de novo on the Earth.

Recent research has shown, however, that RNA nucleotides can be formed without the need for pure ribose. Importantly, the starting materials for the reaction can utilize starting materials that are considered prebiotically plausible, and provide high yields of RNA nucleotides. These results have greatly bolstered the argument that RNA nucleotides may have been found in abundance on the early Earth.


Assuming the presence of pools of RNA nucleotides, how did long strands of RNA form on the early Earth?  Ribozyme function is likely to require strands of RNAs that are composed of at least 30-40 nucleotides.  Research from James Ferris' group at Rensselaer Polytechnic Institute suggests that the formation of long strands of RNA may have been catalyzed by clays such as montmorillonite.  The charged clay surface attracts the nucleotides and the increased local concentration of nucleotides causes bond formation between nucleotides, forming a polymer of RNA (illustrated in the animation on left). 

Another possibility is that strands of RNA could have formed in salty ice water. David Deamer's lab at the University of California at Santa Cruz has found that the process of freezing a dilute solution of chemically activated RNA nucleotides causes the nucleotides to become concentrated as ice crystals form, eventually resulting in the formation of strands of RNA.


Even in the absence of enzymatic catalysts, single-stranded RNAs may have been able to copy strands of RNA through template-directed polymerization. This process is shown in the animation on the left, and is based on experiments performed in Jack Szostak's Lab (MGH/Harvard) using chemically activated nucleotides.

This process of non-enzymatic replication, however, is likely to have been slow and error-prone. Eventually, this mechanism of RNA replication is likely to have been replaced by a more reliable catalyst, such as a ribozyme. Scientists hypothesize that a ribozyme that was capable of making copies of other RNAs, called a replicase, evolved very early in life's history.

The animation on the lower left shows a theoretical replicase copying a template strand of RNA.  While the structure of the replicase  shown in the animation is based on an existing ribozyme that is capable of carrying out the basic steps of a replication reaction, a true replicase that is capable of copying an RNA copy of itself has not yet been isolated in a laboratory. Recently, however, the Hollinger group (MRC, UK) discovered an ice-water stabilized RNA polymerase ribozyme that is capable of copying strands of RNA that were over 200 basepairs long - longer than the ribozyme itself - suggesting that a self-replicating RNA is indeed possible.

Under the proper temperature and salt conditions, double-stranded RNA can undergo strand separation.  Since the two strands are complements of each other (and not exact duplicates), only one of the two strands will be able to refold into an active replicase.  The other strand can act as a template for further rounds of replication to create more replicases.

Next: The role of membranes in the protocell.

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