An international team of researchers with members from Freie Universität Berlin has made an important contribution to our understanding of the incorporation of the essential trace element selenium into proteins. Using single particle cryo electron microscopy, the researchers from Charité – Universitätsmedizin Berlin, the Max Planck Institute for Molecular Genetics, Rutgers University, New Jersey, USA, and the University of Illinois, Chicago, USA, succeeded in visualizing the first steps in selenoprotein synthesis in eukaryotes. The study published in the peer-reviewed journal Science illustrated for the first time how the mammalian ribosome is recoded during selenoprotein synthesis in order to enable insertion of the twenty-first proteinogenic amino acid selenocysteine.

“Our 3D reconstructions show that essential factors in selenoprotein synthesis form an extended network of interactions on the ribosome and in doing so directly integrate ribosomal elements,” says lead author Dr. Tarek Hilal, researcher at the Department of Biology, Chemistry, Pharmacy and the BioSupraMol Core Facility at Freie Universität Berlin. “Highly specific proteins – the selenocysteinyl-tRNA and one selenocysteine-specific regulatory RNA element, the SECIS element – interact in order to prepare the ribosome for selenoprotein synthesis.”

The trace element selenium is essential to human health. When encapsulated in the amino acid selenocysteine, it constitutes a key component in proteins that control a variety of different cellular and metabolic processes in living creatures. In the human body, 25 selenoproteins have been identified which play a role in many vital processes such as thyroid hormone production, detoxifying chemically reactive byproducts in cells, and immune defense. Selenium deficiencies are thought to give rise to serious conditions like diabetes and cancer, while genetic defects in selenoprotein synthesis can have grave consequences during embryonic development.

“Our study helps to put together the individual pieces of a puzzle that have emerged from years of research to create an intriguing overall picture,” says Dr. Hilal. “We were able to demonstrate fundamental differences in the recoding process underlying selenoprotein synthesis of humans and bacteria, and hope that we have laid the groundwork for the development of new therapies for illnesses related to selenium deficiencies.”

The study is available to read here:

Hilal, T., Killam, B. Y., Grozdanović, M., Dobosz-Bartoszek, M., Loerke, J., Bürger, J., Mielke, T., Copeland, P. R., Simonović, M., & Spahn, C. M. T. (2022). Structure of the mammalian ribosome as it decodes the selenocysteine UGA codon. Science, 376(6599), 1338–1343. https://doi.org/10.1126/science.abg3875

Contact

Tarek Hilal, PhD, Freie Universität Berlin, Institute of Chemistry and Biochemistry, Research Center of Electron Microscopy; Core Facility BioSupraMol; Laboratory for Structural Biochemistry, Berlin, Germany, Tel.: +49 30 838 650 99, Email: tarek.hilal@fu-berlin.de