Mass spectrometry of oligonucleotides and nucleic acids

New concepts in mass spectrometry measurements and interpretation

Mass spectrometry of oligonucleotides and nucleic acids

Natural modifications of RNA

Our genes contain all the necessary information to fabricate the constituents of our cells, but one of the mysteries of Life is how each cell can know when to fabricate the appropriate constituents. A cell on our finger does not express the same genes as a cell in our stomach, and gene expression requires regulation mechanisms. At the molecular level, the regulation is due to reversible changes in three-dimensional structures in response to the environment. Here we will investigate how the stability of RNA molecules is modulated by small chemical modifications. On our genes, the changes in chemical modifications in response to the environment is called the epigenetic regulation. By analogy, the set of chemical modifications on RNA is often called the “epitranscriptomic” pattern. Besides understanding the normal state of DNA or RNA modifications and how they change with the environment, it is also extremely important to understand the abnormal states that can lead to diseases. In terms of human health, the RNA modification status has key roles in pathologies such as cancer, neuronal disorders, and mitochondrial diseases. This is a growing field, with new regulation mechanisms and implications discovered every day.

Project: There is a bottleneck, however, in terms of methodologies available for the biologists to investigate the modification profiles. Our objective is to develop novel approaches that will allow us to map all the modifications present simultaneously on an intact DNA or RNA molecule, locate them precisely, and understand which combinations of modifications changes the stability of the three-dimensional structures. These methodological developments will require addressing some fundamental questions in the field of mass spectrometry, and tackling these questions will be the object of the present project.

Sequence and higher-order structure of synthetic oligonucleotides

Ultimately, the research above has the potential to open new avenues towards understanding epigenetic and epitranscriptomic regulation, but also towards safer DNA or RNA-based therapies, and in that sense our research is use-inspired.

Mass Spectrometry for Biophysics