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TranSplice

ERC Starting Grant project (2025-2029)

Kinetoplastids are a family of flagellate protists that includes numerous parasitic species responsible for serious human diseases such as sleeping sickness, Chagas disease, and leishmaniasis. These unicellular eukaryotes have a unique cellular and molecular biology that differs from that of the majority of other organisms, making their study both fascinating and essential for combating the diseases they cause.

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With TranSplice, we aim to the study an essential yet little understood molecular mechanism: SL trans-splicing. This process enables kinetoplastids to generate their messenger RNAs (mRNAs) from long polycistronic precursors by adding a small RNA molecule, the 'Spliced Leader' (SL), to the 5' end of each mRNA via a unique machinery called the trans-spliceosome. Although this machinery is essential for gene expression, the lack of structural information and the high divergence of its RNA and protein elements have hindered a mechanistic understanding of how kinetoplastids employ SL trans-splicing to generate their entire mRNA transcriptome.

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Our methodology

Using a combination of genome editing, high-resolution cryo-electron microscopy, AI-based interactome analyses, and in vivo assays, we investigate the SL snRNP biogenesis and the central mechanism of trans-splicing orchestrated by the highly divergent kinetoplastid trans-spliceosome.

Our Team

Funded by

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© 2025 by Arnaud Vanden Broeck

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