Mistranslating tRNA variants have anticodon- and sex-specific impacts on Drosophila melanogaster.

IF 2.1 3区 生物学 Q3 GENETICS & HEREDITY G3: Genes|Genomes|Genetics Pub Date : 2024-09-23 DOI:10.1093/g3journal/jkae230
Joshua R Isaacson, Matthew D Berg, Jessica Jagiello, William Yeung, Brendan Charles, Judit Villén, Christopher J Brandl, Amanda J Moehring
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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.

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错误翻译的 tRNA 变体对黑腹果蝇具有反密码子和性别特异性影响。
转运核糖核酸(tRNA)对决定翻译的特异性至关重要。tRNA 基因突变会导致氨基酸错误地结合到新生多肽中,这一过程被称为翻译错误。由于翻译错误会根据氨基酸替换的类型产生不同的影响,我们的目标是比较不同的翻译错误 tRNASer 变体对苍蝇发育、寿命和行为的影响。我们建立了两个错译蝇系,一个是在缬氨酸密码子上错置丝氨酸的 tRNASer 变体(V→S),另一个是在苏氨酸密码子上错置丝氨酸的 tRNASer 变体(T→S)。虽然两种错误翻译的 tRNA 都会增加发育时间和发育致死率,但影响的严重程度因氨基酸替换和性别而异。V→S 变体延长了胚胎、幼虫和蛹的发育时间,而 T→S 只延长了幼虫和蛹的发育时间。与对照组相比,含有这两种翻译错误的 tRNA 的雌性(而非雄性)的解剖畸形明显增多。由于错误翻译会破坏细胞翻译和蛋白稳态,我们还测试了 tRNA 变异影响苍蝇寿命的假设。有趣的是,翻译错误的雌蝇寿命延长,而翻译错误的雄蝇寿命不受影响。与延迟神经变性和误译的有益影响相一致的是,误译的雌雄蝇随着年龄的增长,运动能力都有所提高。鉴于tRNA变体在人类中的普遍存在,错误翻译的tRNA变体能够对苍蝇的生理和行为产生积极和消极的影响,这对人类健康具有重要意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
G3: Genes|Genomes|Genetics
G3: Genes|Genomes|Genetics GENETICS & HEREDITY-
CiteScore
5.10
自引率
3.80%
发文量
305
审稿时长
3-8 weeks
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.
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