Mitochondrial translation systems that break the rules

打破规则的线粒体翻译系统

• 批准号: RGPIN-2017-05411
• 负责人: Lang, BerndFranz
• 金额: $ 8.74万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=744379
• 关键词: Mitochondrial; translation; systems; break; rules

Mitochondrial translation systems that break the rulesEukaryotes (i.e. organisms such as animals, plants, and fungi whose cells carry a nucleus) evolved from a mixture of various life forms. Best known is the mitochondrion, the powerhouse of the eukaryotic cell, which goes back to a bacterial symbiont that was acquired by the ancestor of eukaryotes about one billion years ago. This organelle still possesses its own small genome and its own machineries for basic molecular processes including protein synthesis. However, in most eukaryotes, the bacterial ancestry of mitochondria is barely perceptible, since this organelle is exceptionally fast-evolving, often resulting in dramatic changes of basic molecular processes. This has earned mitochondria the reputation as Nature's most advanced evolutionary laboratory'. The objective of our research program is to investigate such innovations at the molecular-genetics and genomics levels, and to understand how they came about. The current focus of our research program is on novelties in mitochondrial protein synthesis, notably two extraordinary phenomena. 1. Invention' of new genetic codes. We have shown previously how mitochondria of yeast have invented new translation-code variants, changing rules how gene sequences are translated into protein. Our bioinformatics tools predict additional similar cases across yeast relatives. We propose to validate these new predictions biochemically, and to investigate their molecular and evolutionary underpinning.2. Translational jumping. We have found recently that a group of yeast (Magnusiomycetes) does not follow conventional rules for translating genes via messenger RNA into protein. Their mitochondrial genes contain numerous short sequence insertions (byps') that normally would block translation. The machinery in Magnusiomycetes mitochondria ignores' these inserts by jumping over them. We propose to investigate the evolutionary origin of byps, their genetic mobility, and the biochemical mechanism of translational bypassing.Investigation of novelties discovered in simple species such as yeasts has been often the first step towards recognizing similar phenomena in more complex species such as humans or plants. Further, insights into unconventional protein synthesis might teach us how to control this process with benefits for human health, agriculture and environment. Requiring a trans-disciplinary research approach, the proposed projects will be highly suited for training students and highly-qualified research personnel.

打破规则的线粒体翻译系统真核生物（即细胞携带细胞核的动物、植物和真菌等生物体）是从各种生命形式的混合物进化而来的。最著名的是真核细胞的发电站，它可以追溯到大约10亿年前真核生物祖先获得的细菌共生体。这个细胞器仍然拥有自己的小基因组和自己的基本分子过程，包括蛋白质合成的机器。然而，在大多数真核生物中，线粒体的细菌祖先几乎不可察觉，因为这种细胞器非常快速地进化，经常导致基本分子过程的戏剧性变化。这为线粒体赢得了“自然界最先进的进化实验室”的美誉。我们研究计划的目标是在分子遗传学和基因组学水平上研究这些创新，并了解它们是如何产生的。我们的研究项目目前的重点是线粒体蛋白质合成的新颖性，特别是两个非凡的现象。1.新的遗传密码的发明。我们之前已经展示了酵母的线粒体如何发明新的编码变体，改变了基因序列翻译成蛋白质的规则。我们的生物信息学工具预测了酵母亲戚中的其他类似病例。我们建议从生物化学的角度验证这些新的预测，并研究它们的分子和进化基础。平移跳跃我们最近发现，一组酵母菌（Magnusiomycetes）不遵循传统的规则，通过信使RNA将基因翻译成蛋白质。它们的线粒体基因包含许多短序列插入（byps），通常会阻止翻译。Magnusiomycetes线粒体中的机器通过跳过它们而忽略这些插入物。我们建议研究byps的进化起源，它们的遗传流动性，以及翻译旁路的生化机制。在简单物种如酵母中发现的新奇现象的研究往往是认识更复杂物种如人类或植物中类似现象的第一步。此外，对非常规蛋白质合成的深入了解可能会教我们如何控制这一过程，从而对人类健康、农业和环境有益。需要跨学科的研究方法，拟议的项目将非常适合培养学生和高素质的研究人员。