Un-natural mRNAs modified with sulfur atoms boost efficient protein synthesis

July 16, 2020

Since mRNAs play a key role in protein synthesis in vivo, the use of mRNAs as medicines and for in vitro protein synthesis has been desired. In particular, mRNA therapeutics hold the potential for application to vaccine therapy(1) against coronaviruses and are being developed. However, the efficiency of protein production with mRNAs in the natural form is not sufficient enough for certain purposes, including application to mRNA therapeutics. Therefore, mRNA molecules allowing for efficient protein production have been required to be developed.

A ribosome(2) repeats the following three steps to synthesize a protein in vivo using an mRNA as a template (translation reaction): 1) Initiation step: A ribosome binds to an mRNA to form a translation initiation complex; 2) Elongation step: The ribosome moves on the mRNA and links amino acids to synthesize a protein; and 3) Termination step: The protein synthesis process concludes, and the ribosome is liberated. In the translation reaction cycle, the initiation step takes the longest time.

Collaborative research by a group of Nagoya University consisting of Professor Hiroshi Abe, Research Assistant Professor Naoko Abe, and graduate student Daisuke Kawaguchi with Yoshihiro Shimizu, a team leader at RIKEN, has succeeded in the development of modified messenger RNAs (mRNAs). The modified mRNA contains sulfur atoms in the place of oxygen atoms of phosphate moieties of natural mRNAs. It is capable of supporting protein synthesis at increased efficiency. They discovered that modified mRNAs accelerated the initiation step of the translation reactions and improved efficiency of protein synthesis by at least 20 times compared with that using natural-form mRNAs."

This method is expected to be used for large-scale synthesis of proteins as raw materials for the production of biomaterials. Moreover, the application of the results obtained in this study to eukaryotic translation systems enables the efficient production of mRNA therapeutics for protein replacement therapy(3) 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 can guide a future direction of the molecular design of modified mRNAs.
This study was supported by the Strategic Basic Research Program CREST of the Japan Science and Technology Agency (JST).

(1) Vaccine therapy

A method of administering a protein antigen to individuals to elicit antibodies that can reduce the susceptibility to infectious diseases. In the case of an mRNA vaccine, an mRNA for in vivo expression of an antigen protein is administered, and then antibodies are produced against the expressed antigen protein.

(2) Ribosome

Multicomponent machinery providing a place where sequence information of an mRNA is read, and a protein is synthesized based on the sequence information while migrating on the mRNA. A ribosome is composed of ribosomal proteins and ribosomal RNAs.

(3) Protein replacement therapy

A treatment method that aims at improvement by supplementing protein from the outside when the deficiency of proteins (enzymes, etc.) is a cause of an illness.

Japan Science and Technology Agency

Related Protein Articles from Brightsurf:

The protein dress of a neuron
New method marks proteins and reveals the receptors in which neurons are dressed

Memory protein
When UC Santa Barbara materials scientist Omar Saleh and graduate student Ian Morgan sought to understand the mechanical behaviors of disordered proteins in the lab, they expected that after being stretched, one particular model protein would snap back instantaneously, like a rubber band.

Diets high in protein, particularly plant protein, linked to lower risk of death
Diets high in protein, particularly plant protein, are associated with a lower risk of death from any cause, finds an analysis of the latest evidence published by The BMJ today.

A new understanding of protein movement
A team of UD engineers has uncovered the role of surface diffusion in protein transport, which could aid biopharmaceutical processing.

A new biotinylation enzyme for analyzing protein-protein interactions
Proteins play roles by interacting with various other proteins. Therefore, interaction analysis is an indispensable technique for studying the function of proteins.

Substituting the next-best protein
Children born with Duchenne muscular dystrophy have a mutation in the X-chromosome gene that would normally code for dystrophin, a protein that provides structural integrity to skeletal muscles.

A direct protein-to-protein binding couples cell survival to cell proliferation
The regulators of apoptosis watch over cell replication and the decision to enter the cell cycle.

A protein that controls inflammation
A study by the research team of Prof. Geert van Loo (VIB-UGent Center for Inflammation Research) has unraveled a critical molecular mechanism behind autoimmune and inflammatory diseases such as rheumatoid arthritis, Crohn's disease, and psoriasis.

Resurrecting ancient protein partners reveals origin of protein regulation
After reconstructing the ancient forms of two cellular proteins, scientists discovered the earliest known instance of a complex form of protein regulation.

Sensing protein wellbeing
The folding state of the proteins in live cells often reflect the cell's general health.

Read More: Protein News and Protein Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.