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.

概括氨基酰基-TRNA合成酶（ARSS）建立遗传密码的规则，每个规则氨基酸附着在同源tRNA上。此过程中的错误导致误导，这可能对细胞有毒。大约一半的ARS具有校对（或编辑）水解错误的AA-TRNA的功能，并证明非蛋白酶氨基酸构成对忠诚的最大威胁开始出现。在Musier-Forsyth实验室的早期工作专注于我们发现II类Prolyl-tRNA合成酶（PRORS）编辑的发现。这导致了在转移编辑域（INS）和演示是INS域。随后我们发现了单域同源物在细菌中很普遍，近年来，我们在该领域的重点已经转变几乎完全是为了理解这些INS样域在tRNA编辑中的功能。但是，有关这些推定的Trans-的生理功能的许多开放性问题保留编辑蛋白。此MIRA应用中描述的研究的总体目标是要揭示不断增长的跨编辑蛋白家族的特定功能，称为 ins超级家族。这个多样化但普遍保守的家庭现在有着坚实的和积累体外结构功能知识库，这强烈支持保持翻译忠诚。我们对这些更广泛的生理作用的了解蛋白质，尤其是在真核生物中，仍处于起步阶段，刚刚开始揭示更广泛的角色比以前预期的。这项工作将解决这个主要差距。

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.