title: Aminoacylation of Plasmodium falciparum tRNA(Asn) and insights in the synthesis of asparagine repeats.
abstract: Genome sequencing revealed an extreme AT-rich genome and a profusion of asparagine repeats associated with low complexity regions (LCRs) in proteins of the malarial parasite Plasmodium falciparum. Despite their abundance, the function of these LCRs remains unclear. Because they occur in almost all families of plasmodial proteins, the occurrence of LCRs cannot be associated with any specific metabolic pathway; yet their accumulation must have given selective advantages to the parasite. Translation of these asparagine-rich LCRs demands extraordinarily high amounts of asparaginylated tRNA(Asn). However, unlike other organisms, Plasmodium codon bias is not correlated to tRNA gene copy number. Here, we studied tRNA(Asn) accumulation as well as the catalytic capacities of the asparaginyl-tRNA synthetase of the parasite in vitro. We observed that asparaginylation in this parasite can be considered standard, which is expected to limit the availability of asparaginylated tRNA(Asn) in the cell and, in turn, slow down the ribosomal translation rate when decoding asparagine repeats. This observation strengthens our earlier hypothesis considering that asparagine rich sequences act as "tRNA sponges" and help cotranslational folding of parasite proteins. However, it also raises many questions about the mechanistic aspects of the synthesis of asparagine repeats and about their implications in the global control of protein expression throughout Plasmodium life cycle.
authors.affiliation: From the Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, Institut de Biologie Moléculaire et Cellulaire, 15 rue René Descartes, 67084 Strasbourg cedex, France and.
authors.forename: Denis
authors.initials: D
authors.lastname: Filisetti
authors.forename: Anne
authors.initials: A
authors.lastname: Théobald-Dietrich
authors.forename: Nassira
authors.initials: N
authors.lastname: Mahmoudi
authors.forename: Joëlle
authors.initials: J
authors.lastname: Rudinger-Thirion
authors.forename: Ermanno
authors.initials: E
authors.lastname: Candolfi
authors.forename: Magali
authors.initials: M
authors.lastname: Frugier
mesh_terms: D000595:Amino Acid Sequence; D000604:Amino Acyl-tRNA Synthetases / Q000378:metabolism; D001216:Asparagine / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000201:enzymology / Q000378:metabolism*; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D043903:Pyrococcus abyssi / Q000201:enzymology; D012348:RNA, Transfer, Asn / Q000096:biosynthesis / Q000378:metabolism*; D020449:Repetitive Sequences, Amino Acid; D046249:Transfer RNA Aminoacylation
chemical_list: D001426:Bacterial Proteins; D015800:Protozoan Proteins; D012348:RNA, Transfer, Asn; D001216:Asparagine; D000604:Amino Acyl-tRNA Synthetases
keywords: Aminoacyl tRNA Synthesis; Asparagine Repeats; Low Complexity Regions; Plasmodium; Protein Folding; Transfer RNA (tRNA); Translation