1. Peculiarities of aminoacyl-tRNA synthetases from trypanosomatids
- Author
-
Florian Bernard, Yaser Hashem, Denis Dupuy, Camila Parrot, Marie Sissler, Luc Moulinier, and Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,[SDV]Life Sciences [q-bio] ,Trans-splicing ,MTS, mt targeting sequence ,Computational biology ,Biology ,Biochemistry ,Amino Acyl-tRNA Synthetases ,03 medical and health sciences ,chemistry.chemical_compound ,Cytosol ,RNA, Transfer ,aaRSs, aminoacyl-tRNA synthetases ,Complementary DNA ,Animals ,Humans ,aminoacyl-tRNA synthetase ,MARS, multi-aaRS complex ,NTD, N-terminal domain ,Amino Acid Sequence ,Amino Acids ,Leishmaniasis ,Molecular Biology ,Gene ,Phylogeny ,ComputingMilieux_MISCELLANEOUS ,Leishmania ,chemistry.chemical_classification ,trans-splicing ,Multiple sequence alignment ,Sequence Homology, Amino Acid ,030102 biochemistry & molecular biology ,Aminoacyl tRNA synthetase ,C-terminus ,Cell Biology ,species-specific insertions/extensions ,CTD, C-terminal domain ,Mitochondria ,3. Good health ,Amino acid ,kinetoplastids ,MSA, multiple sequence alignment ,030104 developmental biology ,chemistry ,Transfer RNA ,mt, mitochondrial ,Research Article - Abstract
Trypanosomatid parasites are responsible for various human diseases, such as sleeping sickness, animal trypanosomiasis, or cutaneous and visceral leishmaniases. The few available drugs to fight related parasitic infections are often toxic and present poor efficiency and specificity, and thus, finding new molecular targets is imperative. Aminoacyl-tRNA synthetases (aaRSs) are essential components of the translational machinery as they catalyze the specific attachment of an amino acid onto cognate tRNA(s). In trypanosomatids, one gene encodes both cytosolic- and mitochondrial-targeted aaRSs, with only three exceptions. We identify here a unique specific feature of aaRSs from trypanosomatids, which is that most of them harbor distinct insertion and/or extension sequences. Among the 26 identified aaRSs in the trypanosome Leishmania tarentolae, 14 contain an additional domain or a terminal extension, confirmed in mature mRNAs by direct cDNA nanopore sequencing. Moreover, these RNA-Seq data led us to address the question of aaRS dual localization and to determine splice-site locations and the 5'-UTR lengths for each mature aaRS-encoding mRNA. Altogether, our results provided evidence for at least one specific mechanism responsible for mitochondrial addressing of some L. tarentolae aaRSs. We propose that these newly identified features of trypanosomatid aaRSs could be developed as relevant drug targets to combat the diseases caused by these parasites.
- Published
- 2021