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Published on: September 27, 2015
Ambiguous decoding of the CUG codon alters the functionality of the Candida albicans translation initiation factor 4E
Zuzana Feketová1, Tomás Masek, Václav Vopálenský
1Department of Genetics and Microbiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.
Abstract:
The eukaryotic translation initiation factor 4E is an essential and highly conserved protein. As a part of the translational machinery, it plays a key role in the recruitment of mRNA via binding to its m(7)GpppN 5' terminal cap structure. The opportunistic human pathogen Candida albicans is the only known eukaryotic organism with the ability to survive defects in mRNA capping, which suggests unique features of its eIF4E protein. Here, we provide the first experimental evidence of the function of the C. albicans putative gene orf19.7626 as an eIF4E protein. We also show that Ca4E(Leu116) and Ca4E(Ser116) protein variants, both of which occur naturally in C. albicans due to the ambiguous decoding of the CUG(116) codon, display different sensitivities to elevated temperature. Our results clearly point to the importance of the S4-H4 loop for the function of the Ca4E translation initiation factor, and suggest the possible regulatory role of the codon-reading ambiguity within this loop in C. albicans. We proved Saccharomyces cerevisiae as a useful tool organism for studies of C. albicans translation initiation apparatus.
Insights
Candida albicans possesses a unique eukaryotic translation initiation factor 4E (eIF4E) enabling survival despite mRNA capping defects. This study identifies its function and reveals temperature-sensitive variants linked to codon ambiguity.
Area of Science:
- Molecular Biology
- Mycology
- Genetics
Background:
- Eukaryotic translation initiation factor 4E (eIF4E) is crucial for mRNA recruitment via cap binding.
- Candida albicans exhibits unique mRNA capping capabilities, suggesting distinct eIF4E features.
- The CUG codon ambiguity in C. albicans leads to naturally occurring protein variants.
Purpose of the Study:
- To experimentally validate the function of the C. albicans gene orf19.7626 as an eIF4E.
- To investigate the functional differences between Ca4E(Leu116) and Ca4E(Ser116) variants.
- To explore the role of the S4-H4 loop and codon ambiguity in C. albicans eIF4E function.
Main Methods:
- Gene function validation using Saccharomyces cerevisiae as a model organism.
- Analysis of protein variant function under varying temperature conditions.
- Investigating the structural and functional significance of the S4-H4 loop.
Main Results:
- orf19.7626 was confirmed as the functional eIF4E in C. albicans.
- Ca4E(Leu116) and Ca4E(Ser116) variants showed differential sensitivity to elevated temperatures.
- The S4-H4 loop was identified as critical for Ca4E function.
Conclusions:
- The study provides the first experimental evidence for C. albicans eIF4E function.
- Codon-reading ambiguity and the S4-H4 loop may regulate translation initiation in C. albicans.
- Saccharomyces cerevisiae serves as an effective model for studying C. albicans translation.
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