Identification of host tRNAs preferentially recognized by the Plasmodium surface protein tRip.

Autor:	Cela M; Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR 9002, F-67000Strasbourg, France., Théobald-Dietrich A; Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR 9002, F-67000Strasbourg, France., Rudinger-Thirion J; Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR 9002, F-67000Strasbourg, France., Wolff P; Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR 9002, F-67000Strasbourg, France., Geslain R; Laboratory of tRNA Biology, Department of Biology, College of Charleston, Charleston, SC, USA., Frugier M; Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR 9002, F-67000Strasbourg, France.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2021 Oct 11; Vol. 49 (18), pp. 10618-10629.
DOI:	10.1093/nar/gkab769
Abstrakt:	Malaria is a life-threatening and devastating parasitic disease. Our previous work showed that parasite development requires the import of exogenous transfer RNAs (tRNAs), which represents a novel and unique form of host-pathogen interaction, as well as a potentially druggable target. This import is mediated by tRip (tRNA import protein), a membrane protein located on the parasite surface. tRip displays an extracellular domain homologous to the well-characterized OB-fold tRNA-binding domain, a structural motif known to indiscriminately interact with tRNAs. We used MIST (Microarray Identification of Shifted tRNAs), a previously established in vitro approach, to systematically assess the specificity of complexes between native Homo sapiens tRNAs and recombinant Plasmodium falciparum tRip. We demonstrate that tRip unexpectedly binds to host tRNAs with a wide range of affinities, suggesting that only a small subset of human tRNAs is preferentially imported into the parasite. In particular, we show with in vitro transcribed constructs that tRip does not bind specific tRNAs solely based on their primary sequence, hinting that post-transcriptional modifications modulate the formation of our host/parasite molecular complex. Finally, we discuss the potential utilization of the most efficient tRip ligands for the translation of the parasite's genetic information. (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu