Wednesday, 24 June 2015

Lost In Translation

The roles of mRNA and tRNA in protein synthesis
The creation of a protein is no simple affair. Even in the simplest organisms, the prokaryotes, it still involves several precisely controlled steps. Firstly genetic information coded in DNA must be transcribed into messenger RNA (mRNA). This is then transported to ribosomes where transfer RNAs (tRNA) carrying amino acids bind to the mRNA, translating the sequence of bases in RNA to a sequence of amino acids, a polypeptide. Finally this polypeptide undergoes post translational changes to give it the specific 3D structure required for its function.

How this sequence of transcription and translation evolved was unclear. A possible explanation is the RNA world hypothesis. This states that prior to the formation of cellular life there existed life-like chemical systems in which energy and information was exchanged, but in the absence of membranes or proteins. Yet our understanding of how the RNA world transitioned into a more contemporary state of nucleic acids (DNA and RNA) in close association with amino acids, polypeptides and proteins has been woolly until recently. A team of researchers from the UNC School of Medicine has shown that this association likely existed early on in the process of forming life.

'Our work shows that the close linkage between the physical properties of amino acids, the genetic code, and protein folding was likely essential from the beginning, long before large, sophisticated molecules arrived on the scene,' said Charles Carter from UNC School of Medicine. 'This close interaction was likely the key factor in the evolution from building blocks to organisms.' By examining the physical properties of the 20 amino acids used by cells, such as their polarity, it was found that there was a relationship between those properties and the genetic code.

Aminoacyl tRNA synthetases catalyse the
formation of tRNAs bonded to amino acids
Polypeptides must fold to form a protein and the rules of the folding process are governed by physical properties such as size and polarity. Previous research has demonstrated that the rules of folding change consistently as temperature changes. Therefore the relationship between the genetic code and protein folding remains stable over a range of temperatures; vital due to the higher temperatures of the early Earth and and fluctuating temperatures involved in making the RNA world functional. The research led by Carter focused on something different: enzymes called aminoacyl tRNA synthetases.

Aminoacyl tRNA synthetases catalyse the binding of amino acids to tRNA. The aminoacyl tRNA products then bind to mRNA and allowing the amino acids to bind together into a polypeptide, the precursor to a protein. 'Think of tRNA as an adapter,' said Carter. 'One end of the adapter carries a particular amino acid; the other end reads the genetic blueprint for that amino acid in messenger RNA. Each synthetase matches one of the twenty amino acids with its own adapter so that the genetic blueprint in messenger RNA faithfully makes the correct protein every time.'

The analysis showed that the two different ends of tRNA molecules contain independent codes or rules that specify which amino acid to select. The end of tRNA that carried the amino acid sorted amino acids according to size. The other end of the tRNA molecules selected amino acids according to polarity. 'Translating the genetic code is the nexus connecting pre-biotic chemistry to biology,' said Carter. We can now say that the genetic code and its translation to proteins evolved due to the simple physical properties of the amino acids involved. Ultimately this suggests that the RNA world is an incomplete hypothesis. Instead it should perhaps be renamed the Peptide RNA world.