A multiple aminoacyl-tRNA synthetase complex that enhances tRNA-aminoacylation in african trypanosomes

Igor Cestari, Savitha Kalidas, Severine Monnerat, Atashi Anupama, Margaret A. Phillips, Kenneth Stuart

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)4872-4888
Number of pages17
JournalMolecular and Cellular Biology
Volume33
Issue number24
DOIs
StatePublished - 2013

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Transfer RNA Aminoacylation
Amino Acyl-tRNA Synthetases
Trypanosomiasis
Trypanosoma brucei brucei
Parasites
Aminoacylation
Multiprotein Complexes
Enzymes
Growth
RNA Interference
Transfer RNA
Mitochondria
Cytoplasm
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology
  • Medicine(all)

Cite this

A multiple aminoacyl-tRNA synthetase complex that enhances tRNA-aminoacylation in african trypanosomes. / Cestari, Igor; Kalidas, Savitha; Monnerat, Severine; Anupama, Atashi; Phillips, Margaret A.; Stuart, Kenneth.

In: Molecular and Cellular Biology, Vol. 33, No. 24, 2013, p. 4872-4888.

Research output: Contribution to journalArticle

Cestari, Igor ; Kalidas, Savitha ; Monnerat, Severine ; Anupama, Atashi ; Phillips, Margaret A. ; Stuart, Kenneth. / A multiple aminoacyl-tRNA synthetase complex that enhances tRNA-aminoacylation in african trypanosomes. In: Molecular and Cellular Biology. 2013 ; Vol. 33, No. 24. pp. 4872-4888.
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