One Template, Two Peptides

Scientists from the University of Tokyo have developed a method of reprogramming the genetic code such that a single mRNA template can yield two different peptides.

AsianScientist (Jul 1, 2014) – Scientists have developed a method that allows two different peptides to be translated from the same mRNA template sequence, a finding which could lead to the development of new drug candidates. This research has been published in Nature Chemical Biology.

Manipulating protein expression has so far focused on the translation step, altering the sequence of the genetic template. The new approach developed by Professor Hiroaki Suga from the University of Tokyo focuses instead on the translation machinery, modifying both the transfer RNA (tRNA) molecules and the ribosome itself.

tRNA molecules are clover leaf-shaped structures which match amino acids to their corresponding codons on the genetic template. At the 3′ end of every tRNA molecule, there is an invariant sequence of three bases, CCA (where C is cytosine and A is adenine). The adenine of this invariant sequence is attached to the amino acid, while the cytosines are required for binding to the ribosome at positions 2251, 2252 and 2253, all guanines.

By introducing complementary mutations to the invariant CCA tail and the corresponding ribosomal residues, Prof. Suga and his research team were able to reprogram the genetic code, synthesizing a peptide with non-natural amino acids.

Furthermore, they demonstrated that it is possible to express two different peptides from the same genetic template by attaching different amino acids to the mutated tRNAs. In effect, the research group developed a modified translation system that uses an artificially designed genetic code.

This novel method for genetic code reprogramming could be applied to the synthesis of non-standard peptides containing non-standard amino acids, which has potential applications in drug development.

The article can be found at: Terasaka et al. (2014) An orthogonal ribosome-tRNA pair via engineering of the peptidyl transferase center.

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Source: University of Tokyo.
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Rebecca did her PhD at the National University of Singapore where she studied how macrophages integrate multiple signals from the toll-like receptor system. She was formerly the editor-in-chief of Asian Scientist Magazine.

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