title: A multiple aminoacyl-tRNA synthetase complex that enhances tRNA-aminoacylation in African trypanosomes.
abstract: The genes for all cytoplasmic and potentially all mitochondrial aminoacyl-tRNA synthetases (aaRSs) were identified, and all those tested by RNA interference were found to be essential for the growth of Trypanosoma brucei. Some of these enzymes were localized to the cytoplasm or mitochondrion, but most were dually localized to both cellular compartments. Cytoplasmic T. brucei aaRSs were organized in a multiprotein complex in both bloodstream and procyclic forms. The multiple aminoacyl-tRNA synthetase (MARS) complex contained at least six aaRS enzymes and three additional non-aaRS proteins. Steady-state kinetic studies showed that association in the MARS complex enhances tRNA-aminoacylation efficiency, which is in part dependent on a MARS complex-associated protein (MCP), named MCP2, that binds tRNAs and increases their aminoacylation by the complex. Conditional repression of MCP2 in T. brucei bloodstream forms resulted in reduced parasite growth and infectivity in mice. Thus, association in a MARS complex enhances tRNA-aminoacylation and contributes to parasite fitness. The MARS complex may be part of a cellular regulatory system and a target for drug development.
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Cestari
authors.forename: Savitha
authors.initials: S
authors.lastname: Kalidas
authors.forename: Severine
authors.initials: S
authors.lastname: Monnerat
authors.forename: Atashi
authors.initials: A
authors.lastname: Anupama
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Phillips
authors.forename: Kenneth
authors.initials: K
authors.lastname: Stuart
mesh_terms: D000595:Amino Acid Sequence; D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry / Q000502:physiology*; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D017124:Conserved Sequence; D007700:Kinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000502:physiology; D021381:Protein Transport; D015800:Protozoan Proteins / Q000502:physiology*; D016053:RNA, Protozoan / Q000378:metabolism*; D012343:RNA, Transfer / Q000378:metabolism*; D046249:Transfer RNA Aminoacylation; D014346:Trypanosoma brucei brucei / Q000201:enzymology* / Q000502:physiology
chemical_list: D009097:Multienzyme Complexes; D015800:Protozoan Proteins; D016053:RNA, Protozoan; D012343:RNA, Transfer; D000604:Amino Acyl-tRNA Synthetases