Wednesday, 24 June 2015

Updating The RNA World

In 2013 I reported on a remarkable discovery made by Charles Carter from the UNC School of Medicine. He found that the two families of proteins involved in the translation of the genetic code into proteins shared a common core of amino acids. Upon extracting these amino acid cores, Carter found that they still had the ability to catalyse the reactions involved in protein synthesis. He gave them the name urzymes, 'ur' meaning first. The original blog post can be found here:

Their results suggested that urzymes evolved from simpler peptide precursors which had co-evolved with RNA in what Carter dubbed the Peptide RNA world hypothesis. In my previous blog post, I reported on more recent work by Carter in which he found additional evidence to support the Peptide RNA world hypothesis. The evidence suggested that genetic code and its translation to proteins evolved due to the simple physical properties of the amino acids involved; co-evolution of peptides and RNA. The blog post can be found here:

Now Carter has revolutionised our view of the RNA world for a third time. He returned to looking at the two families of enzymes involved in translation. Known as aminoacyl tRNA synthetases, they catalyse the binding of amino acids to tRNA to form aminoacyl tRNAs. These then bind to mRNA to create a chain of amino acids, a polypeptide - the precursor to a protein. One family of aminoacyl tRNA synthetases handle the binding of 10 of the 20 amino acids used by cells. The other family deals with the other 10 amino acids.

Carter and a team of researchers deconstructed the two families of enzymes. They found that their catalytic activity came from the same chains of 46 amino acids. These chains, which comprised 5 to 10% of the protein, were the parts which bind to ATP, a compound required as an energy source for most biological reactions, including the linkage of amino acids to tRNA. Carter dubbed these catalytic fragments protozymes, 'protos' meaning 'first' in Ancient Greek. The next step was synthesising artificial protozymes and examining their catalytic activity.

This was done by creating a gene which coded for the relevant amino acid chains. This gene was encoded in DNA, a double stranded nucleic acid. The double strand structure makes DNA more stable than RNA and as such DNA is used as a means of long term storage of genetic information. This is in contrast to single stranded RNA which is unstable and is only used to convey short term genetic information from DNA to sites of protein synthesis. In DNA, one strand is the coding strand and the other is the template strand. Only the coding strand is transcribed and translated.

The artificial protozyme gene, however, was different in that both strands were transcribed and translated. One strand gave rise to the artificial protozyme analogue of the natural protozymes from one family of aminoacyl tRNA synthetases. The other strand gave rise to the artificial protozyme analogue of natural protozymes from the other family of aminoacyl tRNA synthetases. The ability for a single gene to give rise to two different protein products by the utilisation of both the coding and the template strand was predicted in 1994. Carter's work represents the first direct experimental confirmation of this prediction.

When the artificial protozymes were tested for catalytic activity, it was found that they were just as functional as the natural protozymes derived from the two aminoacyl tRNA synthetase families. What this suggests is that the two families also originally derived from a single gene where both the coding and the template strand were utilised to create independent products. 'This doesn't yet solve the central chicken and the egg problem,' said Carter. 'Even the designed protozyme requires a ribosome to synthesize it and lead to protein creation. But what we've shown is that blueprints for life actually contained more information than anyone had realized because both strands of the ancestral gene were responsible for encoding the two classes of synthetases needed for the creation of proteins.'