Joshua R Isaacson, Matthew D Berg, Jessica Jagiello, William Yeung, Brendan Charles, Judit Villén, Christopher J Brandl, Amanda J Moehring
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引用次数: 0
Abstract
Transfer RNAs (tRNAs) are vital in determining the specificity of translation. Mutations in tRNA genes can result in the misincorporation of amino acids into nascent polypeptides in a process known as mistranslation. Since mistranslation has different impacts, depending on the type of amino acid substitution, our goal here was to compare the impact of different mistranslating tRNASer variants on fly development, lifespan, and behaviour. We established two mistranslating fly lines, one with a tRNASer variant that misincorporates serine at valine codons (V→S) and the other that misincorporates serine at threonine codons (T→S). While both mistranslating tRNAs increased development time and developmental lethality, the severity of the impacts differed depending on amino acid substitution and sex. The V→S variant extended embryonic, larval, and pupal development whereas the T→S only extended larval and pupal development. Females, but not males, containing either mistranslating tRNA presented with significantly more anatomical deformities than controls. Since mistranslation disrupts cellular translation and proteostasis, we also tested the hypothesis that tRNA variants impact fly lifespan. Interestingly, mistranslating females experienced extended lifespan whereas mistranslating male lifespan was unaffected. Consistent with delayed neurodegeneration and beneficial effects of mistranslation, mistranslating flies from both sexes showed improved locomotion as they aged. The ability of mistranslating tRNA variants to have both positive and negative effects on fly physiology and behaviour has important implications for human health given the prevalence of tRNA variants in humans.
期刊介绍:
G3: Genes, Genomes, Genetics provides a forum for the publication of high‐quality foundational research, particularly research that generates useful genetic and genomic information such as genome maps, single gene studies, genome‐wide association and QTL studies, as well as genome reports, mutant screens, and advances in methods and technology. The Editorial Board of G3 believes that rapid dissemination of these data is the necessary foundation for analysis that leads to mechanistic insights.
G3, published by the Genetics Society of America, meets the critical and growing need of the genetics community for rapid review and publication of important results in all areas of genetics. G3 offers the opportunity to publish the puzzling finding or to present unpublished results that may not have been submitted for review and publication due to a perceived lack of a potential high-impact finding. G3 has earned the DOAJ Seal, which is a mark of certification for open access journals, awarded by DOAJ to journals that achieve a high level of openness, adhere to Best Practice and high publishing standards.