The Ongoing Quest to Crack the Genetic Code for Protein Production

Mol Cell. 2020 Oct 15;80(2):193-209. doi: 10.1016/j.molcel.2020.09.014. Epub 2020 Oct 2.


Understanding the genetic design principles that determine protein production remains a major challenge. Although the key principles of gene expression were discovered 50 years ago, additional factors are still being uncovered. Both protein-coding and non-coding sequences harbor elements that collectively influence the efficiency of protein production by modulating transcription, mRNA decay, and translation. The influences of many contributing elements are intertwined, which complicates a full understanding of the individual factors. In natural genes, a functional balance between these factors has been obtained in the course of evolution, whereas for genetic-engineering projects, our incomplete understanding still limits optimal design of synthetic genes. However, notable advances have recently been made, supported by high-throughput analysis of synthetic gene libraries as well as by state-of-the-art biomolecular techniques. We discuss here how these advances further strengthen understanding of the gene expression process and how they can be harnessed to optimize protein production.

Keywords: codon usage; heterologous protein production; mRNA stability; transcription; translation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Algorithms
  • Animals
  • Biotechnology
  • Genetic Code*
  • Humans
  • Protein Biosynthesis / genetics*
  • RNA Stability
  • Transcription, Genetic