Melnikov, S. V., Rivera, K. D., Ostapenko, D., Makarenko, A., Sanscrainte, N. D., Becnel, J. J., Solomon, M. J., Texier, C., Pappin, D. J., Soll, D. (July 2018) Error-prone protein synthesis in parasites with the smallest eukaryotic genome. Proc Natl Acad Sci U S A, 115 (27). E6245-6253. ISSN 0027-8424
Abstract
Microsporidia are parasitic fungi-like organisms that invade the interior of living cells and cause chronic disorders in a broad range of animals, including humans. These pathogens have the tiniest known genomes among eukaryotic species, for which they serve as a model for exploring the phenomenon of genome reduction in obligate intracellular parasites. Here we report a case study to show an apparent effect of overall genome reduction on the primary structure and activity of aminoacyl-tRNA synthetases, indispensable cellular proteins required for protein synthesis. We find that most microsporidian synthetases lack regulatory and eukaryote-specific appended domains and have a high degree of sequence variability in tRNA-binding and catalytic domains. In one synthetase, LeuRS, an apparent sequence degeneration annihilates the editing domain, a catalytic center responsible for the accurate selection of leucine for protein synthesis. Unlike accurate LeuRS synthetases from other eukaryotic species, microsporidian LeuRS is error-prone: apart from leucine, it occasionally uses its near-cognate substrates, such as norvaline, isoleucine, valine, and methionine. Mass spectrometry analysis of the microsporidium Vavraia culicis proteome reveals that nearly 6% of leucine residues are erroneously replaced by other amino acids. This remarkably high frequency of mistranslation is not limited to leucine codons and appears to be a general property of protein synthesis in microsporidian parasites. Taken together, our findings reveal that the microsporidian protein synthesis machinery is editing-deficient, and that the proteome of microsporidian parasites is more diverse than would be anticipated based on their genome sequences.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Microsporidia Muller's ratchet aminoacyl-tRNA synthetases genome erosion mistranslation |
| Subjects: | organs, tissues, organelles, cell types and functions > cell types and functions > cell types > eukaryote organs, tissues, organelles, cell types and functions > cell types and functions > cell types > eukaryote organs, tissues, organelles, cell types and functions > cell types and functions > cell types > eukaryote bioinformatics > genomics and proteomics > genetics & nucleic acid processing > genomes |
| CSHL Authors: | |
| Communities: | CSHL labs > Pappin lab |
| Depositing User: | Matt Covey |
| Date: | 3 July 2018 |
| Date Deposited: | 20 Jun 2018 20:55 |
| Last Modified: | 15 Nov 2023 18:27 |
| PMCID: | PMC6142209 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/36751 |
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