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

Lookup NU author(s): Dr Sergey MelnikovORCiD

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This is the final published version of an article that has been published in its final definitive form by National Academy of Sciences, 2018.

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Abstract

© 2018 National Academy of Sciences. All Rights Reserved.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.

Publication metadata

Author(s): Melnikov SV, Rivera KD, Ostapenko D, Makarenko A, Sanscrainte ND, Becnel JJ, Solomon MJ, Texier C, Pappin DJ, Soll D

Publication type: Article

Publication status: Published

Journal: Proceedings of the National Academy of Sciences of the United States of America

Year: 2018

Volume: 115

Issue: 27

Pages: E6245-E6253

Print publication date: 03/07/2018

Online publication date: 18/06/2018

Acceptance date: 23/05/2018

Date deposited: 16/07/2020

ISSN (print): 0027-8424

ISSN (electronic): 1091-6490

Publisher: National Academy of Sciences

URL: https://doi.org/10.1073/pnas.1803208115

DOI: 10.1073/pnas.1803208115

PubMed id: 29915081

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