Progress in Understanding the Interaction between Metabolic Enzymes and RNA

doi:10.13523/j.cb.2308034

China Biotechnology

2024, Vol. 44

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

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

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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

Received: 22 August 2023 Published: 03 April 2024

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

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

Fig.1 Schematic representation of different RNA-metabolic enzyme interaction modes A: RNA binding may affect the localization of the enzyme to subcellular structures B: When the RNA binds to the enzyme, it can further influence its interaction with other subunits C: RNA can act as a bridge between multiple enzymes within a pathway

Table 1 Examples of metabolic enzymes identified as RBP in the RNA interactome studies

Fig.2 The workflow of CLIP-seq

Fig.3 Aconitase1(ACO1)functions as RNA-binding metabolic enzyme A: When iron is deficient, the cuboid iron-sulfur cluster is disaggregated and the inactivated IRP1 binds to the IREs to regulate the intracellular iron concentration B: Under iron-sufficient conditions, IRP1 functions as a cytosolic cisaconitase by assembling a 4Fe-4S cluster

Fig.4 The function of GAPDH as a RNA-binding protein in lymphocytes A: Binding of GAPDH to ARE in the 3'UTR of IFN-γ mRNA inhibits IFN-γ translation in cells B: After activation of T cells and switching to aerobic glycolysis, GAPDH engages primarily in the glycolytic pathway


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