Modification of the mRNA with phosphorothioate increases the speed of translation initiation and molecular designs are optimized for high translation efficiency. This result provides a useful guide to molecular design to improve the amount of translation by chemical modification of the mRNA. Credit: Nagoya University.
Since mRNAs play a key role in protein synthesis in vivo, the use of mRNAs as drugs and for protein synthesis in vitro has been desired. In particular, mRNA therapeutics has the potential of application to coronavirus vaccine therapy and is being developed. However, the efficiency of the production of proteins with mRNA in a natural way is not sufficient for certain purposes, including the therapeutic application of mRNA. Therefore, it has been required that mRNA molecules be developed that allow efficient protein production.
A ribosome repeats the following three steps to synthesize a protein in vivo using an mRNA as a template (translation reaction): 1) Start step: a ribosome binds to an mRNA to form a translation initiation complex; 2) Elongation step: the ribosome moves on the mRNA and unites the amino acids to synthesize a protein; and 3) Termination step: the protein synthesis process ends and the ribosome is released. In the translation reaction cycle, the initiation step takes the longest.
Collaborative research conducted by a group at Nagoya University, consisting of Professor Hiroshi Abe, Research Assistant Professor Naoko Abe, and graduate student Daisuke Kawaguchi with Yoshihiro Shimizu, team leader at RIKEN, has been successful in developing Modified messenger RNA (mRNA). The modified mRNA contains sulfur atoms instead of oxygen atoms from natural mRNA phosphate residues. It is capable of supporting protein synthesis with greater efficiency. They found that the modified mRNAs sped up the initiation step of translation reactions and improved the efficiency of protein synthesis at least 20-fold compared to using mRNA naturally.
This method is expected to be used for large-scale protein synthesis as raw material for biomaterial production. Furthermore, the application of the results obtained in this study to eukaryotic translation systems allows the efficient production of mRNA therapies for protein replacement therapy to contribute to medical treatments. Furthermore, there are virtually no previous reports on the molecular design of highly functional mRNAs; therefore, the successful design achieved in this study may guide a future direction for the molecular design of modified mRNAs.
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Hiroshi Abe et al. Modification of mRNA phosphorothioate accelerates the rate of translation initiation, providing more efficient protein synthesis, Angewandte Chemie International Edition (2020). DOI: 10.1002 / anie.202007111
Provided by the Japan Science and Technology Agency (JST)
Citation: Sulfur-atom-modified synthetic mRNAs increase efficient protein synthesis (2020, July 16) retrieved on July 17, 2020 from https://phys.org/news/2020-07-synthetic-mrnas-sulfur- atoms-boost.html
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