Self-replicating RNA

Chemical replication of oligonucleotides led to the evolution of self-replicating RNA molecules. 

Until now, most of the RNA-world literature has been assuming - tacitly or unconsciously - that ribozymes or self-replicating RNA were there to start... 

The division of function between DNA (genetic information storage) and protein (catalysis) was, according to the RNA world hypothesis, a later development. New variants of self-replicating RNA molecules developed, with the additional ability to catalyze the condensation of amino acids into peptides. Occasionally, the peptide (s) thus formed would reinforce the self-replicating ability of the RNA, and the pair—RNA... 

Some time after the evolution of this primitive protein-synthesizing system, there was a further development DNA molecules with sequences complementary to the self-replicating RNA molecules took over the function of conserving the genetic information, and RNA molecules evolved to play roles in protein synthesis. (We explain in Chapter 8 why DNA is a more stable molecule than RNA and thus a better repository of inheritable information.) Proteins proved to be versatile catalysts and, over time, took over that function. Lipidlike compounds in the primordial soup formed relatively impermeable layers around self-replicating collections of molecules. The concentration of proteins and nucleic acids within these lipid enclosures favored the molecular interactions required in self-replication. 

Review of progress toward the laboratory evolution of a self-replicating RNA. 

This discussion. .. has, in a sense, focused on a straw man the myth of a self-replicating RNA molecule that arose de novo from a soup of random polynucleotides. Not only is such a notion unrealistic in light of our current understanding of prebiotic chemistry, but it should strain the credulity of even an optimist s view of RNA s catalytic potential...Without evolution it appears unlikely that a self-replicating ribozyme could arise, but without some form of self-replication there is no way to conduct an evolutionary search for the first, primitive self-replicating ribozyme. 

RNA has proven to be a remarkably malleable tool in the hands of biochemists, and a satisfactory RNA-dependent RNA polymerase ribozyme will probably be developed in the laboratory eventually. When that happens, it will be the culmination of at least a decade s worth of directed efforts, using complex combinations of rational design and in vitro evolution. It will be an important demonstration that further strengthens the case that an RNA World could have existed, but it will also show that RNA polymerase ribozymes do not appear to be a simple functionality that is likely to appear de novo from a naive population of RNA molecules. The possibility of a self-replicating RNA system less sophisticated than a general RNA-dependent RNA polymerase ribozyme cannot be eliminated. 

Subsequent research influenced by these experiments led many scientists to believe that the concentration of organic molecules in the primordial, nutrientladen, warm ponds (which may have been tidal pools, puddles, shallow lakes, or deep-sea hot springs) increased progressively over time. Eventually more complex molecules formed, such as carbohydrates, lipids, proteins, and nucleic acids. The complexity gap between simple nucleic acids and self-replicating RNA or DNA is, however, large therefore, some scientists have theorized that as-... 

The problem here is to accept the idea that a self-replicating RNA family formed spontaneously by itself—an assumption which, at the state of our knowledge on the prebiotic biosynthesis of mononucleotides and their polymerization, comes close to blind faith. It is possible that the research of the next future will show that the spontaneous formation of a RNA self-replicating family has some scientific basis. At the present time, instead of waiting, it is perhaps right to look for other alternatives. 

The first theory is that life started as a self replicating RNA single strand, that lined up free nucleotides and ligated sequentially in proper 3 -5 phosophodiester bonds, then the two strands would separate and cycle. This theory, obviously driven by the symmetry of double stranded DNA and RNA helices, has not yet worked (7). 

Self-replicating RNA molecules, one of which can direct protein synthesis... 

No. Despite much work to find a self-replicating RNA, the replication always requires the presence of protein. Recent work by David P. Bartel at MIT is showing some promise toward finding an RNA replicase ribozyme (Science 292[5520] 1319). The fact that an RNA replicase may be produced in the laboratory does not, of course, prove that the ribozyme existed in nature. 

Direct autocatalysis occurs in biological polymerizations, such as DNA and RNA replication. In normal biological processes, RNA is produced from DNA. The RNA acts as the carrier of genetic information in peptide synthesis. However, RNA has been found to be able to replicate itself, for example, with the assistance of the Q/li replicase enzyme. Bauer and McCaskill have created traveling fronts in populations of short self-replicating RNA variants (Bauer ct ah, 1989 McCaskill and Bauer, 1993). If a solution of monomers of triphosphorylated adenine, gua-... 

Several labs have made nucleotide chains that compete and even evolve,.., M. P. Robertson and G. R Joyce. Highly efficient self-replicating RNA enzymes. 2014. Chetn Biol. 21(2), p. 238. DOl 10.1016/j.chembiol.2013.12.004. 

---