Team:SJTU-BioX-Shanghai/Project/Subproject1

Rare-Codon Switch

Codon degeneration indicates that more than one codon can be used to encode an amino acid. Every species has codon usage bias. For one species, some codons are rarely used(less than 1%). These codons are called rare codons.

Fig 1.When expressing heterogenous protein, researchers usually want to get rid of the negative effects brought by codon usage bias.

Codon usage and tRNA amount are closely related. When heterogenous protein is expressed, differences in codon usage in mRNA may impede translation because one or more tRNAs are rare in the population, especially when there are multiple consecutive rare codons at the N-terminus of a coding sequence. This has proposed a new way to control protein expression on translational level.

In E.coli, the rarest used codon is AGG for Arg. By adding AGG codons to the site close to initial codon and regulating the abundance of rare tRNA, we can regulate protein biosynthesis on translational level.

Key Words

Rare codon: codon that is used rarely or infrequently in the genome

Rare tRNA: the low-abundant tRNA that can decode rare codon

aaRS: aminoacyl tRNA synthetases that charges cognate tRNA with a specific amino acid

Introduction

We design a Rare-Codon Switch controlling protein biosynthesis.

We can control the translation process by controlling how well the ribosome can get through a tandem of rare codons in the target protein's mRNA.

This process can be achieved by controlling

• Modulator: control the amount of charged rare tRNAs that recognize these rare codons. The amount of charged rare tRNA is controlled by two elements:
  • rare tRNA
  • aminoacyl tRNA synthetases (aaRS)

• Reporter: control the number of rare codons in the target protein's mRNA.