tRNA lysidinylation is essential for the minimal translation system in the Plasmodium falciparum apicoplast.

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2025-03-20 DOI:10.1038/s44319-025-00420-w

Rubayet Elahi, Sean T Prigge

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引用次数: 0

Abstract

For decades, researchers have sought to define minimal translation systems to uncover fundamental principles of life and advance biotechnology. tRNAs, essential components of this machinery, decode mRNA codons into amino acids. The apicoplast of malaria parasites contains 25 tRNA isotypes in its organellar genome-the lowest number found in known translation systems. Efficient translation in such minimal systems depends heavily on post-transcriptional tRNA modifications. One such modification, lysidine at the wobble position (C34) of tRNA_CAU, distinguishes between methionine (AUG) and isoleucine (AUA) codons. tRNA isoleucine lysidine synthetase (TilS) produces lysidine, which is nearly ubiquitous in bacteria and essential for cellular viability. Here, we report a TilS ortholog (PfTilS) targeted to the apicoplast of Plasmodium falciparum. We demonstrate that PfTilS activity is essential for parasite survival and apicoplast function, likely due to its role in protein translation. This study is the first to characterize TilS in an endosymbiotic organelle, contributing to research on eukaryotic organelles and minimal translational systems. Moreover, the absence of lysidine in humans highlights a potential target for antimalarial strategies.

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数十年来，研究人员一直在试图定义最基本的翻译系统，以揭示生命的基本原理并推动生物技术的发展。tRNA 是这一机制的重要组成部分，可将 mRNA 密码子解码为氨基酸。疟原虫的细胞质基因组中含有 25 种 tRNA 异型，这是已知翻译系统中最少的。这种最小系统中的高效翻译在很大程度上取决于转录后 tRNA 的修饰。tRNA 异亮氨酸赖氨酸合成酶（TilS）产生赖氨酸，赖氨酸在细菌中几乎无处不在，是细胞存活所必需的。在这里，我们报告了一种针对恶性疟原虫细胞质的 TilS 同源物（PfTilS）。我们证明，PfTilS 的活性对寄生虫的生存和细胞质功能至关重要，这可能是由于它在蛋白质翻译中的作用。这项研究首次描述了内共生细胞器中TilS的特征，为真核生物细胞器和最小翻译系统的研究做出了贡献。此外，人类体内赖氨酸的缺失凸显了抗疟策略的潜在目标。

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

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

期刊介绍： EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry.