Roles of aminoacyl-tRNA synthetase-interacting multi-functional proteins in physiology and cancer

Zhou, Zheng; Sun, Bao; Huang, Shiqiong; Yu, Dongsheng; Zhang, Xiaochuan

doi:10.1038/s41419-020-02794-2

Cited by 40 publications

(38 citation statements)

References 112 publications

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“…AIMP1/p43 protein is a multifunction protein involved in various physiological and pathological processes. AIMP1 is the precursor of EMAP II, which was released after AIMP1 cleavage 70 . Surprisingly, the C-terminal segment of EMAP II are 50% identical to residues 205–364 of p42 protein from S. cerevisiae that was firstly identify as G4p1 a protein that shows a high and specific affinity for G4 nucleic acids 71 .…”

Section: Discussionmentioning

confidence: 99%

Constrained G4 structures unveil topology specificity of known and new G4 binding proteins

Pipier

Devaux

Lavergne

et al. 2021

Sci Rep

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G-quadruplexes (G4) are non-canonical secondary structures consisting in stacked tetrads of hydrogen-bonded guanines bases. An essential feature of G4 is their intrinsic polymorphic nature, which is characterized by the equilibrium between several conformations (also called topologies) and the presence of different types of loops with variable lengths. In cells, G4 functions rely on protein or enzymatic factors that recognize and promote or resolve these structures. In order to characterize new G4-dependent mechanisms, extensive researches aimed at identifying new G4 binding proteins. Using G-rich single-stranded oligonucleotides that adopt non-controlled G4 conformations, a large number of G4-binding proteins have been identified in vitro, but their specificity towards G4 topology remained unknown. Constrained G4 structures are biomolecular objects based on the use of a rigid cyclic peptide scaffold as a template for directing the intramolecular assembly of the anchored oligonucleotides into a single and stabilized G4 topology. Here, using various constrained RNA or DNA G4 as baits in human cell extracts, we establish the topology preference of several well-known G4-interacting factors. Moreover, we identify new G4-interacting proteins such as the NELF complex involved in the RNA-Pol II pausing mechanism, and we show that it impacts the clastogenic effect of the G4-ligand pyridostatin.

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Section: Discussionmentioning

confidence: 99%

Constrained G4 structures unveil topology specificity of known and new G4 binding proteins

Pipier

Devaux

Lavergne

et al. 2021

Sci Rep

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“…Its structure has a catalytic and a noncatalytic domain called AIMP or scaffold proteins that interacts with various regulatory factors in the cell. In addition to participating in cellular homeostasis, they play an important role in antitumor mechanisms [ 17 ]. Any mutation or change in the genes encoding ARS enzymes causes changes in cell function and various diseases.…”

Section: Discussionmentioning

confidence: 99%

A Metabolomic Investigation of Eugenol on Colorectal Cancer Cell Line HT-29 by Modifying the Expression of APC, p53, and KRAS Genes

Ghodousi-Dehnavi

Hosseini

Arjmand

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Colorectal cancer is one of the most lethal cancers with a high mortality rate. Chemotherapy results in drug resistance in some cases; hence, herbal medicines are sometimes used in adjunct with it. Eugenol has been reported to have anti-inflammatory, antioxidant, and anticancer properties. Metabolomics is a study of metabolic changes within an organism using high-throughput technology. The purpose of this research was to investigate the anticancer effects of eugenol and variations in p53, KRAS, and APC gene expression and metabolic changes associated with the abovementioned gene expressions using 1HNMR spectroscopy. The MTT method was used to determine cell viability and its IC50 detected. After treating HT-29 cells with IC50 concentration of eugenol, RNA was extracted and cDNA was obtained from them and the expression of p53, KRAS, and APC genes was measured using the qRT-PCR technique. Metabolites were extracted using the chloroform-ethanol method, lyophilized, and sent for 1HNMR spectroscopy using the 1D-NOESY protocol. Chemometrics analysis such as PLS-DA was performed, and differentiated metabolites were identified using the Human Metabolome Database. Integrated metabolic analysis using the metabolites and gene expression was performed by the MetaboAnalyst website. The observed IC50 for eugenol was 500 μM, and the relative expression of APC and p53 genes in the treated cells increased compared to the control group, and the expression of KRAS oncogene gene decreased significantly. The crucial changes in convergent metabolic phenotype with genes were identified. The results indicate that eugenol exhibits its antitumor properties by targeting a specific biochemical pathway in the cell’s metabolome profile due to changes in genes involved in colon cancer.

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“…It is well known that tRNAs bind to their homologous amino acids through ARS-mediated aminoacylation, thereby transporting amino acids to the ribosome to participate in protein synthesis. In mammalian cells, one part of ARSs exists in free form, while the other part interacts with three ARS-interacting multi-functional proteins (AIMPs) to form a multi-tRNA synthetase complex (MSC) 55 . Intriguingly, ARSs and AIMPs are closely associated with aging and lifespan (Table 2).…”

Section: Trna Aminoacylation In Aging and Lifespanmentioning

confidence: 99%

Roles of tRNA metabolism in aging and lifespan

Zhou

Sun

et al. 2021

Cell Death Dis

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Transfer RNAs (tRNAs) mainly function as adapter molecules that decode messenger RNAs (mRNAs) during protein translation by delivering amino acids to the ribosome. Traditionally, tRNAs are considered as housekeepers without additional functions. Nevertheless, it has become apparent from biological research that tRNAs are involved in various physiological and pathological processes. Aging is a form of gradual decline in physiological function that ultimately leads to increased vulnerability to multiple chronic diseases and death. Interestingly, tRNA metabolism is closely associated with aging and lifespan. In this review, we summarize the emerging roles of tRNA-associated metabolism, such as tRNA transcription, tRNA molecules, tRNA modifications, tRNA aminoacylation, and tRNA derivatives, in aging and lifespan, aiming to provide new ideas for developing therapeutics and ultimately extending lifespan in humans.

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Roles of aminoacyl-tRNA synthetase-interacting multi-functional proteins in physiology and cancer

Cited by 40 publications

References 112 publications

Constrained G4 structures unveil topology specificity of known and new G4 binding proteins

Constrained G4 structures unveil topology specificity of known and new G4 binding proteins

A Metabolomic Investigation of Eugenol on Colorectal Cancer Cell Line HT-29 by Modifying the Expression of APC, p53, and KRAS Genes

Roles of tRNA metabolism in aging and lifespan

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