The gene YEF3 function encoding translation elongation factor eEF3 is partially conserved across fungi

Front Microbiol. 2024 Aug 23:15:1438900. doi: 10.3389/fmicb.2024.1438900. eCollection 2024.

Abstract

Introduction: Translation is a fundamental process of life. In eukaryotes, the elongation step of translation is highly conserved and is driven by eukaryotic translation elongation factors (eEF)1A and eEF2. A significant variation of the elongation is the activity of eukaryotic elongation factor (eEF) 3 in Saccharomyces cerevisiae encoded by the gene yeast elongation factor (YEF3) with orthologs in all fungal species, a few algae, and some protists. In S. cerevisiae, YEF3 is an essential gene and eEF3 plays a critical role in translation elongation, as it promotes binding of the ternary complex acylated-Transfer RNA (tRNA)-eEF1A-Guanosine-5'-triphosphate (GTP) to the aminoacyl (A) site of the ribosome, the release of uncharged tRNAs after peptide translocation, and ribosome recycling. Even though YEF3 was discovered more than 40 years ago, eEF3 has been characterized almost exclusively in S. cerevisiae.

Methods: We undertook an in vivo genetic approach to assess the functional conservation of eEF3 across phylogenetically distant fungal species.

Results: We found that eEF3 from Zygosaccharomyces rouxii and Candida glabrata (both belonging to phylum Ascomycota), Ustilago maydis (phylum Basidiomycota), and Gonapodya prolifera (phylum Monoblepharomycota), but not Aspergillus nidulans (phylum Ascomycota), supported the growth of S. cerevisiae lacking the endogenous YEF3 gene. We also proved that eEF3 is an essential gene in the ascomycetes C. glabrata and A. nidulans.

Discussion: Given that most existing knowledge on fungal translation has only been obtained from S. cerevisiae, our findings beyond this organism showed variability in the elongation process in Fungi. We also proved that eEF3 is essential in pathogenic fungi, opening the possibility of using eEF3 as a target to fight candidiasis.

Keywords: RNA metabolism; YEF3; eEF3; fungal translation; translation elongation; translation evolution.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. GH was supported by the intramural funding program of the National Institute of Cancer (Instituto Nacional de Cancerología, Mexico). CONAHCyT Ph. D. fellowships were awarded to AG (No. 436200) and GM (No. 749487). The study on A. nidulans was supported by Deutsche Forschungsgemeinschaft (DFG) Fi459/19-2. The C. glabrata study was funded in part by CONAHCYT Grant No. CF-2019-610281 to IC.