RNA.world

These RNA World experiments establish that biologically relevant molecules could be produced abiotically. We know that RNA-based enzymes were first hypothesized and later found in nature and that abiotic ribozymes are capable of polymerizing RNA molecules very quickly. In short, ribozyme RNA polymerases do exist and may have been the first genetic information replicators. Ribozyme RNA polymerases satisfy two of our criteria for the bare minimal requirements for the origin of life: replication and change over time.

It's an RNA WORLD ??? Self-Organizing & Replicating Molecules:
After Tom Cech's 1980 discovery of catalytic RNA molecules, biologists proposed a radical hypothesis for the earliest enzymes and genomes were composed of RNA and not protein. The RNA-World hypothesis is based upon ribozymes. The unicellular eukaryote, Tetrathymena, has an RNA intron with the capacity to remove itself for an original RNA and self-spllce the one RNA piece, with a new covalent bond, linking the two loose ends of the excised RNA by catalyzing a ligation reaction. Study of this Tetrhymena ribozyme provides much of the experimental evidence support of the RNA-World hypothesis and RNA as a key player in the origin of life.
Ligation is chemically similar to the task performed by native RNA polymerases. In the lab the Tetrahymena ribozyme produce one trinucleotide CUN and a single base (G) without a P in this reaction. CpU + GPN + ribozyme -----> CpUpN + G + ribozyme Researchers wanted to see how many bases could be polymerized by this self-splicing ribozyme. In experiments to see it the ribozyme would add new nucleotides to an existing short (5 nucleotide) RNA showed it showed some polymerase activity, even in the absence of added RNA dinucleotides and would double the RNA length in about 1 hour, but without adding a G-nulceotides. Its slow rate suggested it is not a robust enough RNA polymerase.
Investigators decided to synthesize some synthetic ribozymes in the laboratory and use directed evolution to isolate new molecules that could polymerize RNA faster. From a big array of trillions synthetic ribozymes, each with slightly different sequences, they looked for increased polymerase rates. [See model to right & select the BLUE one]. By modifying the blue one and selecting until you get the fastest ribozyme polymerase, the researchers produced 25 of the fastest ribozymes that had, all of which had many bases in common. The investigators eventually built one synthetic ribozyme that could catalyze RNA polymerization at about 100 bases per minute, some 700 times faster than the biological one isolated from Tetrahymena. By comparing the old and new ribozyme sequences the investigators could determine which bases were critical for the enhanced function.
These RNA World experiments establish that biologically relevant molecules could be produced abiotically. We know that RNA-based enzymes were first hypothesized and later found in nature and that abiotic ribozymes are capable of polymerizing RNA molecules very quickly. In short, ribozyme RNA polymerases do exist and may have been the first genetic information replicators. Ribozyme RNA polymerases satisfy two of our criteria for the bare minimal requirements for the origin of life: replication and change over time.	back