This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: A study conducted by the University of Liège and Rockefeller University reveals, with near-atomic precision, the three-dimensional structure and function of a gigantic molecular machine essential to the survival of trypanosomatid parasites, which cause serious diseases in humans, animals and plants. The work has been published in Nature Communications.
This discovery sheds light on a biological mechanism that has remained a mystery for nearly 40 years and reveals several features specific to these organisms. Trypanosomatids are parasites responsible for numerous diseases affecting humans, animals and plants. In humans, they cause tropical diseases such as leishmaniasis, sleeping sickness and Chagas disease, which affect several million people worldwide.
Treatments exist, but they remain limited by their efficacy, toxicity or the development of resistance. And this problem extends beyond human health. Other trypanosomatids infect livestock, causing major economic losses, while some species infect crops and significantly reduce agricultural yields.
What makes these parasites so unusual? In our cells, genetic information is first copied into RNA, a kind of draft that must be processed before it can serve as instructions for making proteins. One of the steps in this maturation process is RNA splicing, during which certain sequences, known as introns, are cut out and removed.
"Trypanosomatids use a very specific form of this process, known as Spliced Leader (SL) RNA trans-splicing," explains Arnaud Vanden Broeck, a biologist heading the Laboratory of RNA Structural Biology and Biochemistry at the University of Liège. "In these organisms, conventional intron splicing is extremely rare. Instead, virtually all of their messenger RNAs receive the same short RNA sequence, known as the SL RNA, at their 5' end.
This step is essential for the maturation of their RNAs and therefore for the functioning of their cells." Two factors make this mechanism particularly interesting: It is absolutely essential for the parasite's survival, and it does not exist in this form in humans. This is precisely what makes it a promising target for new treatments, as blocking this step could neutralize the parasite without disrupting our own cells. The machine responsible for this process, known as the trans-spliceosome, is a true molecular factory.
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