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20. Oct. 2021
Gabriel Demo from CEITEC and his colleagues from the University of Massachusetts (USA) and Jefferson University (USA) deciphered a previously unknown mechanism commonly occurring in viruses. The researchers discovered how the ribosome and elongation factor G (EF-G) in bacteria cooperate between each other to induce the change of the reading frame on the messenger RNA containing so called “slippery” sequences. The change of the reading frame is an important mechanism for gene expression in various organisms and enables, for example, the spread of viral infections.
The new findings shed more light on how the change of the reading frame occurs in the ribosomes. Other researchers could build on those findings and design novel drugs inhibiting viral infection. The research findings of Gabriel Demo and his colleagues were recently published in the scientific journal Nature Communications.
Several studies have previously proposed that the change of reading frame (+1 frameshifting) can occur during one of the three stages of the elongation cycle: (1) decoding of a “slippery” sequence, (2) EF-G catalysed translocation, or (3) after translocation and/or EF-G dissociation. The possibility of rearrangements of a frameshifting complex at all three elongation stages remained to be explored and caught the attention of Gabriel Demo and his research team. “The structures presented in our work provide the long-sought snapshots of +1 frameshifting, suggesting that frameshifting truly occurs during EF-G-catalysed translocation,” explains the first author of the study, Gabriel Demo.
The researchers used cryogenic electron microscopy (cryo-EM) technology that allows cooling of the biological samples to cryogenic temperatures and embeds them into an environment of vitreous water. This way they were able to observe the biomolecules (ribosome complexes) at high-resolution and to determine the mechanistic details of the ribosomal frame shift, more specifically the slippery sequence for a +1-frameshift signal. “Our findings demonstrate that the ribosome and EF-G cooperate to induce +1 frameshifting during tRNA-mRNA translocation,” concludes Gabriel Demo.
The research was performed in collaboration with the research groups of Dr. Andrei Korostelev from the University of Massachusetts Medical school, MA, USA, and Dr. Ya-Ming Hou from Jefferson University, PA, USA. This study was supported and funded by Czech Science Foundation, project no. GJ20-16013Y.