Comparative proteomics uncovers low asparagine content in Plasmodium tRip-KO proteins

IUBMB Life. 2024 Dec;76(12):1403-1413. doi: 10.1002/iub.2891. Epub 2024 Jul 4.

Abstract

tRNAs are not only essential for decoding the genetic code, but their abundance also has a strong impact on the rate of protein production, folding, and on the stability of the translated messenger RNAs. Plasmodium expresses a unique surface protein called tRip, involved in the import of exogenous tRNAs into the parasite. Comparative proteomic analysis of the blood stage of wild-type and tRip-KO variant of P. berghei parasites revealed that downregulated proteins in the mutant parasite are distinguished by a bias in their asparagine content. Furthermore, the demonstration of the possibility of charging host tRNAs with Plasmodium aminoacyl-tRNA synthetases led us to propose that imported host tRNAs participate in parasite protein synthesis. These results also suggest a novel mechanism of translational control in which import of host tRNAs emerge as regulators of gene expression in the Plasmodium developmental cycle and pathogenesis, by enabling the synthesis of asparagine-rich regulatory proteins that efficiently and selectively control the parasite infectivity.

Keywords: amino acid usage; transfer RNAs and aminoacyl‐tRNA synthetases; translational control.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acyl-tRNA Synthetases / genetics
  • Amino Acyl-tRNA Synthetases / metabolism
  • Animals
  • Asparagine* / genetics
  • Asparagine* / metabolism
  • Gene Knockout Techniques
  • Malaria / metabolism
  • Malaria / parasitology
  • Plasmodium berghei / genetics
  • Plasmodium berghei / growth & development
  • Plasmodium berghei / metabolism
  • Protein Biosynthesis
  • Proteomics* / methods
  • Protozoan Proteins* / genetics
  • Protozoan Proteins* / metabolism
  • RNA, Transfer / genetics
  • RNA, Transfer / metabolism

Substances

  • Asparagine
  • Protozoan Proteins
  • RNA, Transfer
  • Amino Acyl-tRNA Synthetases