Collaborating with teams from UCLA, University of California, Irvine (UCI), and ShanghaiTech University, Boston University researchers have determined the architecture of the molecular machines that harbor gRNA strands and allow those strands to engage mRNA. Their findings were published in Science.
Identifying these cellular mechanisms could give scientists essential information for treating African sleeping sickness, the disease caused by Trypanosoma. For example, understanding these processes better could lead to the development of treatments that inhibit the RNA editing process, killing the parasite without harming human cells. The collaborative research utilized cryo-electron microscopy and molecular approaches to gain detailed insights into RNA editing. The team found that the editosome, a protein complex, guides changes in RNA through a series of insertions and deletions of uridine.
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In Trypanosoma, RNA editing serves a critical purpose of repairing damaged genes caused by common mutations in the parasite's DNA. Since RNA editing mechanisms differ widely among species, the unique RNA editing mechanisms of Trypanosomes offer an attractive therapeutic target for eradicating the parasite while sparing human cells.
With a deep understanding of the protein structures involved in RNA editing, the researchers' next focus is to identify the enzymes that initiate reactions in the cell. This knowledge will shed light on how these reactions occur and how enzymes modify the RNA sequence.