Error-prone protein synthesis in parasites with the smallest eukaryotic genome

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

URL: https://www.ncbi.nlm.nih.gov/pubmed/29915081
DOI: 10.1073/pnas.1803208115

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: 23 Jul 2018 16:35
Related URLs:
URI: http://repository.cshl.edu/id/eprint/36751

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