mRNA is at the heart of a new fundamental mechanism

  • Research
Published on November 9, 2023 Updated on November 9, 2023

on the October 13, 2023


A team of researchers at IRCAN have discovered a new fundamental mechanism for increased, higher-quality production of an entire family of human proteins. This work, published in the journal Nucleic Acids Research in August 2023, could prove useful in the field of mRNA-based therapies such as vaccines.

Messenger RNA (mRNA) is the hot topic of the moment with mRNA vaccines (for protection against Covid-19 and promising clinical trials in the treatment of certain cancers) and the 2023 Nobel Prize for Medicine or Physiology that was recently awarded to mRNA pioneers. The team of Philippe Lenormand, Roser Buscà and Cercina Onesto, researchers in Dr. Gilles Pagès' team at the Institute for Research on Cancer and Aging in Nice (IRCAN), located at the Centre Antoine Lacassagne, have now discovered that mRNA is at the heart of a new fundamental mechanism that contributes to increased and higher-quality production of a whole family of human proteins.

This mechanism is even more important for proteins involved in pathologies such as cancer. The researchers first identified this mechanism for ERK1/2 signaling proteins, effector kinases of the Ras-Raf-ERK signaling pathway, which play a crucial role in tumor development among other things.
They then realized that ten percent of human proteins were affected by their discovery. For the first time, they showed that the proteins in this family all have a very specific motif at one end of their sequence, called NTAR (for N-Terminal Alanine-Rich). This NTAR motif ensures optimal functioning of the cellular machinery that produces a protein from its mRNA (a process known as translation), by promoting the selection of the proper AUG codon that initiates this translation. It thus increases the production of high-quality, fully functional proteins.

This mechanism sheds light on a complex aspect of the very first steps in the protein translation mechanism, steps that had not been explored since the late 1980s.

This work, described as a scientific breakthrough by the prestigious scientific journal Nucleic Acids Research, was published in August 2023. It will expand our understanding of pathologies involving NTAR proteins and could prove useful in the field of mRNA therapies such as vaccines.