Impact of tRNA-induced proline-to-serine mistranslation on the transcriptome of Drosophila melanogaster.

IF 2.1 3区生物学 Q3 GENETICS & HEREDITY

G3: Genes|Genomes|Genetics Pub Date : 2024-09-04 DOI:10.1093/g3journal/jkae151

Joshua R Isaacson, Matthew D Berg, William Yeung, Judit Villén, Christopher J Brandl, Amanda J Moehring

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引用次数: 0

Abstract

Mistranslation is the misincorporation of an amino acid into a polypeptide. Mistranslation has diverse effects on multicellular eukaryotes and is implicated in several human diseases. In Drosophila melanogaster, a serine transfer RNA (tRNA) that misincorporates serine at proline codons (P→S) affects male and female flies differently. The mechanisms behind this discrepancy are currently unknown. Here, we compare the transcriptional response of male and female flies to P→S mistranslation to identify genes and cellular processes that underlie sex-specific differences. Both males and females downregulate genes associated with various metabolic processes in response to P→S mistranslation. Males downregulate genes associated with extracellular matrix organization and response to negative stimuli such as wounding, whereas females downregulate aerobic respiration and ATP synthesis genes. Both sexes upregulate genes associated with gametogenesis, but females also upregulate cell cycle and DNA repair genes. These observed differences in the transcriptional response of male and female flies to P→S mistranslation have important implications for the sex-specific impact of mistranslation on disease and tRNA therapeutics.

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tRNA 诱导的脯氨酸-丝氨酸错误翻译对黑腹果蝇转录组的影响

错误翻译是指氨基酸错误地结合到多肽中。错误翻译对多细胞真核生物有多种影响，并与多种人类疾病有关。在黑腹果蝇中，丝氨酸转移核糖核酸（tRNA）在脯氨酸密码子（P→S）上错结合丝氨酸对雌雄果蝇的影响不同。这种差异背后的机制目前尚不清楚。在这里，我们比较了雌雄苍蝇对 P→S 误翻译的转录反应，以确定导致性别差异的基因和细胞过程。雄蝇和雌蝇都会下调与 P→S 误翻译有关的各种代谢过程的基因。雄性会下调与细胞外基质组织和对伤口等负面刺激的反应有关的基因，而雌性则会下调有氧呼吸和 ATP 合成基因。两性都上调与配子发生有关的基因，但雌性也上调细胞周期和 DNA 修复基因。观察到的雌雄苍蝇对 P→S 错误翻译的转录反应差异对错误翻译对疾病和 tRNA 治疗的性别特异性影响具有重要意义。

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 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.