Scientists discover new details about RNA editing in single-celled, disease-causing parasite

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Ruslan and Inna Afasizheva have collaborated for many years as molecular biologists at University of Boston and as husband and wife. They have published numerous papers on the interactions between mitochondrial DNA and RNA in the disease-causing parasite Trypanosoma brucei, which has a single-celled structure. Their most recent paper, which was just published in Science, offers a thorough examination of the puzzling process known as RNA editing and may even help treat an incurable illness. Years of research have now resulted in this paper.

Together with colleagues from UCLA, the University of California, Irvine( UCI ), and ShanghaiTech University, they are the first to identify the molecular structures that house gRNA strands and enable them to interact with mRNA in their most recent paper. Scientists may be able to treat African sleeping sickness, a condition brought on by the Trypanosoma, by identifying these cellular mechanisms. African sleeping sickness is typically fatal because it is spread by tsetse flies that harbor the parasite, and many of the available treatments have safety concerns, making molecular studies crucial for the development of new drugs.

We can now begin more extensive research. Since then, we are fully aware of how proteins and RNA interact.

Associate professor of molecular and cell biology at University of Boston’s Henry M. Goldman School of Dental Medicine is Afasizheva.

Afasizhev, a professor of biochemistry at University of Boston Chobanian & amp, Avedisian School of Medicine and the paper’s corresponding author, asserts that if we can stop the editing process, the parasite can be eliminated without harming human cells.

The study of RNA has developed and advanced significantly, as has the ability to study the interior of cells. The couple’s team now has a thorough understanding of RNA editing thanks to cryo-electron microscopy and molecular methods. Their most recent study, which made use of this technology, discovered that a protein complex known as the editosome is in charge of orchestrating gRNA-guided changes that take the form of cascades of insertion and deletion of the chemical element uridine. RNA editing in the Trypanosoma is crucial for repairing a damaged gene. Even though the genetic code is unreadable due to the parasite’s frequent DNA mutations, the edited mRNA still functions as a component of the cell.

In almost all organisms with cells with a nucleus and mitochondria, RNA editing controls many cellular processes. However, according to Afasizhev, there is nothing in common between the RNA editing mechanisms in various organisms, indicating that they evolved for various purposes unique to various species. Since it won’t affect human cells, trypanosomes’ RNA editing mechanisms are an appealing therapeutic target for preventing the parasite from causing disease. The next step in their research is identifying the enzymes that start the reactions in the cell now that they are aware of the protein structures specific to RNA editing in trypanosomes.

The next query, according to Afasizheva, is” How do these reactions take place, how these enzymes reach the substrate, and how do they produce the magnificent work to alter the RNA sequence?”

She and Afasizhev want to add more students to their lab so they can continue to solve this challenging puzzle and embrace technological advancements in their field.

Journal mention:
S. Liu and others The structural underpinnings of mRNA recognition and gRNA stabilization in trypanosomal RNA editing ( 2023 ). Science. Do. org / 10. 126 / science adg4725.

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