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Malaria is a disease that causes several hundred thousand deaths each year in tropical regions. This disease is caused by the bite of an Anopheles mosquito infected with the Plasmodium parasite (falciparum or vivax).

Previously, Magali Frugier’s team (UPR 9002) demonstrated that the infectious form of the parasite (sporozoite) can import exogenous tRNAs and that this import involves the participation of the surface protein tRip (tRNA import protein). In the absence of tRip, parasite development is affected in the blood of the vertebrate host, suggesting that host tRNAs may affect translation and/or regulation of gene expression in Plasmodium.

Orange post-transcriptional modifications are overrepresented while blue modifications are rare in tRip-selected tRNAs. These modifications are clustered in two distinct parts of the tRNA and the entrance of some tRNAs into the parasite could be facilitated.

The objective of the paper published in Nucleic Acids Research, is to understand how host tRNAs are recognized by tRip and whether all tRNAs are recognized with the same efficiency. This work was done in collaboration with the team of Dr. Renaud Geslain (Charleston, USA) who developed the MIST technique (Microarray Identification of Shifted tRNAs). This technique allowed to identify, without structure or sequence bias, the tRNAs selected by tRip among all the tRNAs encoded in the human genome. The authors showed that not all human tRNAs are recognized with the same affinity, suggesting that some specific tRNAs might be imported more efficiently into the parasite than others. Recognition specificity is not sequence or structure dependent but correlates with the presence or absence of certain post-transcriptional modifications of tRNAs. These results are an essential step in understanding the biological role of imported tRNAs in parasite development.

To date, exogenous tRNA import has only been demonstrated in Plasmodium and this singularity makes this mechanism and tRip potential targets for the development of new antimalarial approaches.

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Contact: Dr Magali Frugier,

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