代谢酶与RNA相互作用的研究进展<sup>*</sup>

doi:10.13523/j.cb.2308034

中国生物工程杂志

2024, Vol. 44

Issue (2/3): 124-133 DOI: 10.13523/j.cb.2308034

综述

代谢酶与RNA相互作用的研究进展^*

张竹玉,姜娜,陈瑞冰^**(

)

天津大学药物科学与技术学院天津 300072

Progress in Understanding the Interaction between Metabolic Enzymes and RNA

ZHANG Zhuyu,JIANG Na,CHEN Ruibing^**(

)

School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China

全文: PDF(1162 KB) HTML

摘要：

细胞代谢重编程对维持细胞稳态、细胞生长与增殖等细胞过程发挥着重要作用,并广泛参与恶性转化等病理过程。随着高通量分子检测技术的发展,人们发现有些代谢酶不仅能通过催化细胞内各种生化反应参与细胞代谢调控,同时还能结合RNA分子。这些代谢酶不具备经典的RNA结合域。已有研究显示它们可能通过一种负反馈机制调控其结合mRNA的运输、稳定性或翻译,从而将基因表达调控与细胞代谢联系起来。除此之外,酶的代谢产物也可能参与RNA与代谢酶相互作用的调控。重点从近年来发现的具备RNA结合能力的代谢酶、代谢酶与RNA的相互作用方式、RNA结合蛋白的鉴定与验证、代谢调控机制以及这些代谢酶与RNA相互作用如何调控复杂的细胞活动和疾病的发生发展过程进行综述。

关键词： RNA结合蛋白; 代谢酶; 细胞代谢; 蛋白质组学; 质谱

Abstract:

Cellular metabolic reprogramming plays an important role in maintaining cellular homeostasis, cell growth and proliferation, and is widely involved in pathological processes such as malignant transformation. With the development of high-throughput molecular detection technology, it has been found that some metabolic enzymes can not only participate in the regulation of cellular metabolism by catalyzing a variety of intracellular biochemical reactions, but also bind to RNA molecules. These metabolic enzymes do not have classical RNA-binding domains, and it has been shown that they can regulate the transport, stability, or translation of their binding mRNA through a negative feedback mechanism, thereby linking the regulation of gene expression to cell metabolism. In addition, the metabolites of enzymes may also be involved in the regulation of the interaction between RNA and metabolic enzymes. This study reviews metabolic enzymes with RNA-binding ability, the interaction between metabolic enzymes and RNA, the identification and verification of RNA binding protein, metabolic regulation mechanisms, and how the interaction between these metabolic enzymes and RNA regulates complex cellular activities and the onset and development of disease.

Key words: RNA binding protein Metabolic enzymes Cell metabolism Proteomics Mass spectrometry

收稿日期: 2023-08-22 出版日期: 2024-04-03

ZTFLH:

Q71

基金资助: *国家自然科学基金(21974094);2021年天津市研究生科研创新项目(2021YJSB192)

通讯作者: **电子信箱:rbchen@tju.edu.cn

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引用本文:

张竹玉, 姜娜, 陈瑞冰. 代谢酶与RNA相互作用的研究进展^*[J]. 中国生物工程杂志, 2024, 44(2/3): 124-133.

ZHANG Zhuyu, JIANG Na, CHEN Ruibing. Progress in Understanding the Interaction between Metabolic Enzymes and RNA. China Biotechnology, 2024, 44(2/3): 124-133.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2308034 或 https://manu60.magtech.com.cn/biotech/CN/Y2024/V44/I2/3/124

图1 不同RNA-代谢酶相互作用模式示意图 A:与RNA的结合可能会影响酶在亚细胞结构中的定位 B:当RNA与酶结合时,可以进一步影响酶与其他亚基之间的相互作用 C:RNA可以作为桥梁连接通路中的多个酶

表1 RNA相互作用组研究发现的RNA结合代谢酶

图2 CLIP-seq的实验流程图

图3 胞质顺乌头酸酶1(ACO1)作为RNA结合代谢酶发挥作用 A:铁缺乏时,立方铁硫簇被分解,失活的IRP1与IREs结合,调节细胞内铁浓度 B:在铁充足的情况下,IRP1通过组装结合4Fe-4S簇,作为细胞质内的顺乌头酸酶发挥作用

图4 GAPDH作为淋巴细胞内一种RNA结合蛋白的生物功能 A:GAPDH与IFN-γ mRNA的3'UTR中的ARE结合会抑制IFN-γ在细胞中的翻译;B:T细胞活化并转向有氧糖酵解后,GAPDH主要参与糖酵解途径

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