Saturday, October 31, 2015

"AAAAA Is for Arrested Translation"

In a post by Ruth Williams focusing on recent research results, a study conducted on the halt of protein translation found that multiple adenosine nucleotides in messenger RNA was the reason behind the interruption. The finding contradicted the idea that protein sequences were responsible. The importance behind the failure of the ribosome protein to translate the codon sequences of mRNA into amino acids lies on the fact that the mRNA and developing protein are degraded during the process.
Due to Rachel Green and her research team at Johns Hopkins University School of Medicine, it was found that there is a significance in the difference between mRNA sequences and associated amino acids. Bacterial ribosomes were found to halt on lysines in the presence of AAA codons as opposed to AAG codons. The research team, utilizing human cells, went on to find that reporter gene constructs with lysines encoded by AAA sequences had far less protein production then lysines encoded by AAG, as well as arginines encoded by AGG and CGA codons.
Two outcomes from this research were particularly important- bioinformatic analyses of vertebrate genomes proposed that the AAA codons are not favored evolutionary, and previously thought silent mutations may actually alter protein expression. The AAA sequence was thought to not be favored, being that the chance of lysines encoded by such a sequence was much lower than the chance of being encoded by AAG codons. The rejection of the silent mutation inference to instead be of greater importance, stemmed from mutating AAG codons to AAA codons and finding a decrease in protein expression. The opposite result was found from mutating AAA codons to AAG codons.
It is particularly interesting how failing to discover one tiny aspect of the translation process could later result in finding reasons behind translation failure. This may suggest that silent mutations are even more rare than previously thought, and that perhaps these mutations are simply misunderstood rather than inactive in many processes.

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