更新于：2024-11-01

TRMT5

更新于：2024-11-01

基本信息

别名

KIAA1393、M1G-methyltransferase、TRM5

+ [5]

简介

Involved in mitochondrial tRNA methylation (PubMed:26189817). Specifically methylates the N1 position of guanosine-37 in various tRNAs. Methylation is not dependent on the nature of the nucleoside 5' of the target nucleoside. This is the first step in the biosynthesis of wybutosine (yW), a modified base adjacent to the anticodon of tRNAs and required for accurate decoding.

关联

100 项与 TRMT5 相关的临床结果

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100 项与 TRMT5 相关的转化医学

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0 项与 TRMT5 相关的专利（医药）

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项与 TRMT5 相关的文献（医药）

2024-10-01·Small

Circulating B Cell‐Derived Small RNA Delivered by Extracellular Vesicles: A Dialogue Mechanism for Long‐Range Targeted Renal Mitochondrial Injury in Obesity

Article

作者: Han, Yi ; Wang, Cunchuan ; Yin, Lianghong ; Li, Hongyue ; Meng, Yu ; Hu, Bo ; Liu, Xiayun ; Zheng, Zirun ; Huang, Sibo ; Liu, Huanhuan ; Chen, Ruichang ; Xiao, Zhangzhang ; Liu, Jinfeng ; Ma, Ke ; Yang, Wah ; Li, Xiaqing ; Zhao, Qian

AbstractThe intricate processes that govern the interactions between peripatetic immune cells and distal renal injury in obesity are not fully understood. Employing transcriptomic analysis of circulating extracellular vesicles (EVs), a marked amplification of small RNA (miR‐3960) is discerned within CD3−CD19+ B cells. This RNA is found to be preferentially augmented in kidney tissues, contrasting with its subdued expression in other organs. By synthesizing dual‐luciferase reporter assay with co‐immunoprecipitation analysis, it is pinpointed that miR‐3960 specifically targets the nuclear gene TRMT5, a pivotal actor in the methylation of mitochondrial tRNA. This liaison instigates aberrations in the post‐transcriptional modifications of mitochondrial tRNA, engendering deficiencies within the electron respiratory chain, primarily attributable to the diminution of the mitochondrial bioenergetic compound (NDUFA7) complex I. Such perturbations lead to a compromised mitochondrial respiratory capacity in renal tubular cells, thereby exacerbating tubular injury. In contrast, EV blockade or miR‐3960 depletion markedly alleviates renal tubular injury in obesity. This investigation unveils a hitherto unexplored pathway by which obesity‐induced circulating immune cells remotely manipulate mitochondrial metabolism in target organs. The strategic targeting of obese EVs or infiltrative immune cells and their specifically secreted RNAs emerges as a promising therapeutic avenue to forestall obesity‐related renal afflictions.

2024-07-01·Translational Cancer Research

Novel mitochondrial-related gene signature predicts prognosis and immunological status in glioma

Article

作者: Chen, Guangliang ; Liu, Yongsheng ; Cai, Lize ; Yao, Lin ; Zhang, Kai ; Zhou, Youxin ; Wang, Hao

BackgroundMitochondria are the center of cellular metabolism. The relationship between mitochondria and diseases has also been studied for a long time. However, the prognostic role of mitochondrial-related genes (MRGs) in patients with glioma and their biological effects are still unclear. The aim of the study was to construct a mitochondria-related model to assess prognosis and potential biological effects like immune infiltration, gene pathway and mutation, and give some predictive chemotherapeutic agents.MethodsThe data of 675 patients from The Cancer Genome Atlas (TCGA) database were used to identify MRG signature and construct a prognostic model. After validating its robustness in Chinese Glioma Genome Atlas (CGGA), two risk groups derived from the prognostic model were then conducted with Gene Set Enrichment Analysis (GSEA), immune status, mutation status and chemotherapeutic agents prediction.ResultsThe prognostic model built from six gene signatures can successfully predict the prognosis and reflect clinicopathological characteristics. Patients in high-risk group displayed significantly worse overall survival (OS), immunosuppression effects, and mutation markers with worse prognosis. Twelve chemotherapeutic agents with strongly correlated sensitivity and risk scores were selected as potential agents.ConclusionsThe novel MRG signatures (TYMP, TSFM, MGME1, BOLA3, TRMT5, NDUFA9) can predict prognosis and immunological status in glioma.

2024-03-01·iScience

RNA modification-related genes illuminate prognostic signature and mechanism in esophageal squamous cell carcinoma

Article

作者: Ma, Jieyi ; Guo, Siyao ; Qiu, Hongshen ; Jiang, Xu ; Wang, Juan ; Liu, Lianlian ; Liu, Qianwen ; Zhang, Canfeng ; Wang, Zhaoyu ; Cheng, Maosheng ; Sun, Yucong ; Zheng, Siyi ; Wei, Wei ; Han, Hui ; Huang, Zixin ; Lin, Shuibin ; Zhang, Shuishen ; Zhang, Qiang ; Li, Zhenpeng

Emerging studies have demonstrated the link between RNA modifications and various cancers, while the predictive value and functional mechanisms of RNA modification-related genes (RMGs) in esophageal squamous cell carcinoma (ESCC) remain unclear. Here we established a prognostic signature for ESCC based on five RMGs. The analysis of ESCC clinical samples further verified the prognostic power of the prognostic signature. Moreover, we found that the knockdown of NSUN6 promotes ESCC progression in vitro and in vivo, whereas the overexpression of NSUN6 inhibits the malignant phenotype of ESCC cells. Mechanically, NSUN6 mediated tRNA m⁵C modifications selectively enhance the translation efficiency of CDH1 mRNA in a codon dependent manner. Rescue assays revealed that E-cadherin is an essential downstream target that mediates NSUN6's function in the regulation of ESCC progression. These findings offer additional insights into the link between ESCC and RMGs, as well as provide potential strategies for ESCC management and therapy.

项与 TRMT5 相关的新闻（医药）

2024-07-21

·生物谷

揭秘肥胖肾损新元凶！Small | 暨南大学孟宇团队首次发现B细胞衍生囊泡携miR-3960远程攻击肾线粒体

肥胖症是 21 世纪严重的公共卫生挑战之一。与肥胖相关的肾脏病的发病率也随之增加，其中B细胞在肥胖炎症反应中发挥了重要作用。胞外囊泡(Extracellular vesicles, EVs)及其包含的RNA 是介导细胞间远程调控的重要纳米级载体。富含RNA的EVs在肾脏疾病及线粒体功能障碍中起核心作用，此外，免疫细胞来源的RNA参与疾病的发生发展。然而，B细胞来源的EVs对肾脏的远程调控机制尚不清楚。解析该机制对防止肥胖相关肾损伤进展为不可逆的肾衰竭至关重要。暨南大学附属第一医院孟宇/尹良红/王存川团队在国际纳米研究重要期刊Small发表了题为：“Circulating B Cell-Derived Small RNA Delivered by Extracellular Vesicles: A Dialogue Mechanism for Long-Range Targeted Renal Mitochondrial Injury in Obesity ” 的研究论文。报道了来源于B细胞来源的微小RNA（miR-3960）通过循环EVs的转运，远程调控肾小管上皮细胞内线粒体呼吸链，能够靶向线粒体TRMT5基因，使得tRNA 转录后修饰异常，进而引发线粒体电子呼吸链损伤，这主要归因于线粒体生物能化合物(NDUFA7)复合体I的减少。这种扰动导致肾小管细胞线粒体呼吸能力受损，最终加重肥胖症肾小管损伤。 1. 肥胖病中胞外囊泡是肾小管损伤的重要损伤因子：首先，作者收集了127名患者的血标本和肾脏病理标本进行分析明确BMI升高与肾功能下降有显著相关性。并进一步通过体内实验证明外泌体抑制剂（GW4869）可以明显减轻高脂喂养的肥胖小鼠的肾功能损伤。 2. 肥胖循环胞外囊泡（Obese-EVs）会破坏近端小管上皮细胞（PTECs）的线粒体功能和结构：Obese-EVs可导致 PTECs 中线粒体功能和结构破坏，同时伴有 ATP 生成减少和 ROS 生成增加。 3. 循环B细胞是miR-3960的主要来源细胞，并通过EVs运输至肾脏损害 PTECs 线粒体：二代测序结果显示miR-3960是外泌体中与BMI呈正相关的重要miRNA。肥胖状态下，外周血单个核细胞中CD3− CD19+ B细胞比例上升，miR-3960在CD3− CD19+ B细胞中含量显著增加。因此，作者探索发现肥胖患者血液循环中的B细胞是miR-3960的主要储存库，miR-3960通过Obese-EVs运输至肾脏。进一步在体外转染miR-3960和构建慢病毒miR-3960载体注射至小鼠均发现miR-3960可引起肾小管上皮细胞线粒体结构破坏和功能降低从而导致肾小管上皮细胞坏死。 4. TRMT5/NDUFA7 轴被预测为 miR-3960 的下游通路直接损线粒体呼吸链：通过 RNA-seq 进行转录组分析确认NDUFA7 是下调程度最大的基因。使用包括 Mitocarta (Human)、miRDB、TargetScan 和 miRPath DB 在内的数据库预测了 miR-3960 的靶标是TRMT5。作者进行了双荧光素酶报告基因检测和免疫功沉淀实验说明miR-3960 与 TRMT5 3′UTR 结合并直接调节 TRMT5。 5. TRMT5/NDUFA7轴介导肥胖EVs/miR-3960影响下的肾小管线粒体损伤：以上研究结果引出了一个问题：Obese-EVs/miR-3960/TRMT5/NDUFA7 是否是导致肾小管线粒体损伤的致病因素。作者通过体外实验，将PTEC 与 Obese-EVs 共培养，发现TRMT5 和 NDUFA7 表达降低。并且miR-3960 过表达也会抑制TRMT5 和 NDUFA7 表达，miR-3960 抑制剂使它们的表达恢复到正常水平。体内实验中HFD小鼠或者rAAV9-miR-3960 转染后肾脏组织中均发现TRMT5 和 NDUFA7 表达降低。综上所述，本研究研究发现Obese-EVs/miR-3960/TRMT5/NDUFA7 是导致肾小管线粒体损伤的重要通路。该研究发现，循环中富集RNA的B细胞浸润是肥胖相关肾损伤的始发因素；而B细胞来源EVs的释放能够使B细胞远距离将有害的miR-3960转移至肾小管上皮细胞；其可通过靶向TRMT5基因，并下调NDUFA7表达，导致肾小管细胞的线粒体电子呼吸链损伤。而通过干预外泌体释放或miR-3960表达，可改善肥胖相关肾损伤；因此，本研究最终揭露了肥胖相关肾损伤新机制，有望转化成为临床上治疗肥胖相关肾损伤的新靶点。论文链接： https://doi-org.libproxy1.nus.edu.sg/10.1002/smll.202402526 本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！

临床1期