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Translational quality control by trans-editing domains

通过转编辑域控制翻译质量

基本信息

批准号：
10822416
负责人：
Karin M Musier-Forsyth
金额：
$ 15.65万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-17 至 2026-04-30
项目状态：
未结题

项目摘要

Summary Aminoacyl-tRNA synthetases (ARSs) establish the rules of the genetic code, whereby each amino acid is attached to a cognate tRNA. Errors in this process lead to mistranslation, which can be toxic to cells. Approximately half of the ARSs possess a proofreading (or editing) function to hydrolyze mischarged aa-tRNAs and evidence that non-proteinaceous amino acids pose the greatest threat to fidelity is beginning to emerge. Early work in the Musier-Forsyth lab focused on our discovery of Class II prolyl-tRNA synthetase (ProRS) editing. This led to a mechanistic understanding of the bacterial ProRS posttransfer editing domain (INS) and the demonstration that the INS domain. We subsequently discovered that single-domain INS homologs are widespread in Bacteria and in recent years, our focus in this area has turned almost entirely to understanding the function of these INS-like domains in tRNA editing. However, many open questions regarding the physiological function of these putative trans- editing proteins remain. The overarching goal of the research described in this MIRA application is to uncover the specific functions of a growing family of trans-editing proteins known as the INS superfamily. This diverse yet universally conserved family now has a solid and accumulating in vitro structure-function knowledge base, which strongly supports a role in maintaining translational fidelity. Our knowledge of the broader physiological roles of these proteins, especially in eukaryotes, is still in its infancy and is just beginning to reveal wider roles than previously anticipated. This major gap will be addressed in this work.

总结氨酰-tRNA合成酶（ARS）建立遗传密码的规则，氨基酸连接到同源tRNA。这一过程中的错误会导致误译，对细胞是有毒的。大约一半的ARS拥有校对（或编辑）具有水解错误电荷的aa-tRNA的功能，对忠诚度构成最大威胁的人开始出现。Musier-Forsyth实验室的早期工作重点是我们发现的II类脯氨酰-tRNA合成酶（ProRS）编辑。这导致对细菌ProRS转移后编辑结构域（INS）的机制理解和演示INS域。我们随后发现单域INS 同源物广泛存在于细菌中，近年来，我们在这一领域的重点已经转向这几乎完全有助于理解这些INS样结构域在tRNA编辑中的功能。然而，许多关于这些假定的反式- 编辑蛋白质仍然存在。本MIRA应用程序中描述的研究的总体目标是揭示一个不断增长的反式编辑蛋白家族的特定功能， INS超家族。这个多样化但普遍保守的家族现在有一个坚实的，积累体外结构-功能知识库，这有力地支持了在保持翻译保真度。我们对这些细胞更广泛的生理作用的了解蛋白质，特别是真核生物中的蛋白质，仍处于起步阶段，刚刚开始揭示更广泛的作用，比之前预期的要多。这项工作将处理这一重大差距。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Plant-exclusive domain of trans-editing enzyme ProXp-ala confers dimerization and enhanced tRNA binding.

DOI：
10.1016/j.jbc.2022.102255
发表时间：
2022-09
期刊：
JOURNAL OF BIOLOGICAL CHEMISTRY
影响因子：
4.8
作者：
Byun, Jun-Kyu;Vu, John A.;He, Siou-Luan;Jang, Jyan-Chyun;Musier-Forsyth, Karin
通讯作者：
Musier-Forsyth, Karin

Transfer RNAs: A treasure trove that keeps on giving.