Protein Synthesis In Cells Research Articles

Gly-Leu instead of Gly promoted the proliferation and protein synthesis of chicken intestinal epithelial cells

Gly-Leu instead of Gly promoted the proliferation and protein synthesis of chicken intestinal epithelial cells

Cordycepin, a bioactive compound from Cordyceps spp., moderates Alzheimer’s disease-associated pathology via anti-oxidative stress and autophagy activation

Alzheimer’s causes cognitive dysfunction. This study investigated the neuro-promoting effects of cordycepin on amyloid-beta precursor protein (APP) synthesis in human neuroblastoma SH-SY5Y cells. Cordycepin was found to boost SH-SY5Y cell proliferation and decreased AD pathology. APP, PS1, and PS2 were downregulated whereas ADAM10 and SIRT1 were upregulated by cordycepin. Cordycepin also reduced APP secretion in a dose-dependent manner. Cordycepin alleviated oxidative stress by the upregulation of GPX and SOD, as well as autophagy genes (LC3, ATG5, and ATG12). Cordycepin activity was also found to be SIRT1-dependent. Therefore, cordycepin may relieve the neuronal degeneration caused by APP overproduction, and oxidative stress.

Chemotranscriptomic analysis of 7-hydroxymatairesinol-related effects on MCF7 human breast tumor cells

Introduction. Establishing the effects of anticancer drugs on the transcriptome is an important procedure in postgenomic pharmacology necessary to comprehensively assess the desired and undesirable effects of candidate drugs. Aim: to assess the effects of lignan 7-hydroxymatairesinol (7HMR) on breast tumor cells.Materials and Methods. Chemotranscriptome profiling was carried out in MCF7 cells (breast cancer cell line) after 24-hour incubation with 7HMR. The GEO (Gene Expression Omnibus) database contains samples of data from transcriptomic studies allowing to model dose-dependent compound-related effects on gene expression based on the chemograph-derived combinatorial analysis algorithms. As a result, a panel of genes with altered expression is generated, which are analyzed by the functional linkage method using the international nomenclature of Gene Ontology (GO) linked to biological roles of genes/proteins.Results. Dose-dependent effects of 7HMR on gene transcription (change in transcription by 5 % or more per 1 μmol 7HMR) were established for 3,468 out of 12,700 genes studied. 7HMR significantly reduced the expression of genes involved in maintaining cell proliferation (401 genes including those involved in telomere maintenance), protein synthesis (194 genes) and proteasomal protein degradation (70 genes), energy metabolism in tumor cells (91 genes) and chronic inflammation (148 genes). A decline in the expression of such gene groups retards the processes of proliferation and vital activity along with protecting host body from excessive inflammation. 7HMR contributed to a predominant increase in the transcription of gene groups involved in antitumor activity (more than 100 genes), including the genes involved in maintaining antitumor immunity as well as those mediating the antitumor effects of vitamin D, retinoids, and vitamin C.Conclusion. The revealed changes in gene transcription enhance 7HMR-related effects on proteome proteins and suggest the prospects for using 7HMR for effective and safe prevention and treatment of nodular mastopathy and breast cancer.

Essential role of the amino-terminal region of Drosha for the Microprocessor function

Drosha is a core component of the Microprocessor complex that cleaves primary-microRNAs (pri-miRNAs) to generate precursor-miRNA and regulates the expression of ∼80 ribosomal protein (RP) genes. Despite the fact that mutations in the amino-terminal region of Drosha (Drosha-NTR) are associated with a vascular disorder, hereditary hemorrhagic telangiectasia, the precise function of Drosha-NTR remains unclear. By deleting exon 5 from the Drosha gene and generating a Drosha mutant lacking the NTR (ΔN), we demonstrate that ΔN is unable to process pri-miRNAs, which leads to a global miRNA depletion, except for the miR-183/96/182 cluster. We find that Argonaute 2 facilitates the processing of the pri-miR-183/96/182 in ΔN cells. Unlike full-length Drosha, ΔN is not degraded under serum starvation, resulting in unregulated RP biogenesis and protein synthesis in ΔN cells, allowing them to evade growth arrest. This study reveals the essential role of Drosha-NTR in miRNA production and nutrient-dependent translational control.

An early glycolysis burst in microglia regulates mitochondrial dysfunction in oligodendrocytes under neuroinflammation

Metabolism and energy processes governing oligodendrocyte function during neuroinflammatory disease are of great interest. However, how varied cellular environments affect oligodendrocyte activity during neuroinflammation is unknown. We demonstrate that activated microglial energy metabolism controls oligodendrocyte mitochondrial respiration and activity. Lipopolysaccharide/interferon gamma promote glycolysis and decrease mitochondrial respiration and myelin protein synthesis in rat brain glial cells. Enriched microglia showed an early burst in glycolysis. In microglia-conditioned medium, oligodendrocytes did not respire and expressed less myelin. SCENITH revealed metabolic derangement in microglia and O4-positive oligodendrocytes in endotoxemia and experimental autoimmune encephalitogenic models. The early burst of glycolysis in microglia was mediated by PDPK1 and protein kinase B/AKT signaling. We found that microglia-produced NO and itaconate, a tricarboxylic acid bifurcated metabolite, reduced mitochondrial respiration in oligodendrocytes. During inflammation, we discovered a signaling pathway in microglia that could be used as a therapeutic target to restore mitochondrial function in oligodendrocytes and induce remyelination.

Autism- and epilepsy-associated EEF1A2 mutations lead to translational dysfunction and altered actin bundling

Protein synthesis is a fundamental cellular process in neurons that is essential for synaptic plasticity and memory consolidation. Here, we describe our investigations of a neuron- and muscle-specific translation factor, eukaryotic Elongation Factor 1a2 (eEF1A2), which when mutated in patients results in autism, epilepsy, and intellectual disability. We characterize three EEF1A2 patient mutations, G70S, E122K, and D252H, and demonstrate that all three mutations decrease de novo protein synthesis and elongation rates in HEK293 cells. In mouse cortical neurons, the EEF1A2 mutations not only decrease de novo protein synthesis but also alter neuronal morphology, regardless of endogenous levels of eEF1A2, indicating that the mutations act via a toxic gain of function. We also show that eEF1A2 mutant proteins display increased tRNA binding and decreased actin-bundling activity, suggesting that these mutations disrupt neuronal function by decreasing tRNA availability and altering the actin cytoskeleton. More broadly, our findings are consistent with the idea that eEF1A2 acts as a bridge between translation and the actin cytoskeleton, which is essential for proper neuron development and function.

Pigeon during the Breeding Cycle: Behaviors, Composition and Formation of Crop Milk, and Physiological Adaptation.

Pigeon is an important economic poultry species in many countries. As an altricial bird, its growth and development are largely reliant on pigeon milk produced by the crop tissue in the first week. During the breeding cycle, pigeons undergo a series of behavioral changes. Pigeon milk is generally characterized by having high concentrations of proteins and lipids, and a complicated regulatory network is involved in the milk formation. Hormones, especially prolactin, could promote the proliferation of crop epidermal cells and nutrient accumulation. The expression of target genes associated with these important biological processes in the crop epidermis is affected by non-coding RNAs. Meanwhile, signaling pathways, such as target of rapamycin (TOR), Janus kinase/signal transducer and activator of transcription proteins (JAK/STAT), protein kinase B (Akt), etc., influence the production of crop milk by either enhancing protein synthesis in crop cells or inducing apoptosis of crop epidermal cells. In order to adapt to the different breeding periods, pigeons are physiologically changed in their intestinal morphology and function and liver metabolism. This paper reviews the behaviors and physiological adaptations of pigeon during the breeding cycle, the composition of pigeon crop milk, and the mechanism of its formation, which is important for a better understanding of the physiology of altricial birds and the development of artificial crop milk.

The use of apolipoprotein A-I as a transport form of the green fluorescent protein GFP gene in rat hepatocytes

The aim of this study was to investigate the possibility of using apolipoprotein A-I (apo A-I) as a transport form of the green fluorescent protein (GFP) gene into rat hepatocytes.Material and methods. A culture of isolated rat hepatocytes was used as a model. Apo A-I conjugate with fluorescein isothiocyanate (FITC) was obtained by incubation of apo A-I protein with FITC in carbonate buffer pH 9.5 at a ratio of 12.5 μg FITC per 1 mg of protein. Plasmids for pE-GAG transfection with an integrated GFP gene were enriched in the promoter part with cis-elements of the CC(GCC)3-5 type to enhance complex formation with apo A-I. An inverted fluorescence microscope was used for visual analysis of cell fluorescence.Results and discussion. The paper presents evidence of FITC-labeled apo A-I penetration into the cytoplasm and nuclei of rat hepatocytes by receptor-mediated endocytosis. On this basis, it is proposed an attempt to use apo A-I as a means of targeted delivery of plasmid DNA with an integrated GFP gene into the cell. According to the results of fluorescence microscopy, the use of apo A-I as a plasmid DNA transfection agent led to the accumulation of the GFP protein in the cytoplasm of hepatocytes. No fluorescent protein was observed in the absence of apo A-I.Conclusions. The result obtained may indicate the delivery of the GFP gene to the nuclear apparatus of the cell, its expression and GFP protein synthesis.

ʟ-Asparaginases and Their Potential in Biotechnology and Medicine

ʟ-Asparaginase (EC 3.5.1.1) is a key enzyme that hydrolyzes ʟ-asparagine to ʟ-aspartic acid and ammonia. This feature of ʟ-asparaginase is used in anti‑cancer therapy to inhibit protein synthesis in cancer cells. Therefore, ʟ-asparaginase is used as a basis for chemotherapy to treat patients with acute lymphoblastic leukemia in pediatrics. Commercial ʟ-asparaginases for healthcare applications are mainly obtained from Escherichia coli and Erwinia chrysanthemi (renamed to Dickeya dadantii). However, the high prevalence of adverse effects complicates the long‑term clinical use of ʟ-asparaginase, and therefore current research focuses on the search for new enzymes or on modifying the properties of enzymes already known. At the same time, ʟ-asparaginase has become indispensable for the food industry in recent years, when it had been recognized as one of the possible tools for removing ʟ-asparagine from foods that are at risk of acrylamide formation during thermal processing. This review provides an overview of the current use of ʟ-asparaginase and its pitfalls.

Characterization of choroid plexus in the preterm rabbit pup following subcutaneous administration of recombinant human IGF-1/IGFBP-3

Insulin-like growth factor-1 (IGF-1) is essential for normal brain development and regulates essential processes of vascular maturation and stabilization. Importantly, preterm birth is associated with reduced serum levels of IGF-1 as compared to in utero levels. Using a preterm rabbit pup model, we investigated the uptake of systemic recombinant human (rh) IGF-1 in complex with its main binding protein IGF-binding protein 3 (BP-3) to the brain parenchyma via the choroid plexus. Five hours after subcutaneous administration, labeled rhIGF-1/rhIGFBP-3 displayed a widespread presence in the choroid plexus of the lateral and third ventricle, however, to a less degree in the fourth, as well as in the perivascular and subarachnoid space. We found a time-dependent uptake of IGF-1 in cerebrospinal fluid, decreasing with postnatal age, and a translocation of IGF-1 through the choroid plexus. The impact of systemic rhIGF-1/rhIGFBP-3 on IGF-1 receptor activation in the choroid plexus decreased with postnatal age, correlating with IGF-1 uptake in cerebrospinal fluid. In addition, choroid plexus gene expression was observed to increase with postnatal age. Moreover, using choroid plexus in vitro cell cultures, gene expression and protein synthesis were further investigated upon rhIGF-1/rhIGFBP-3 stimulation as compared to rhIGF-1 alone, and found not to be differently altered. Here, we characterize the uptake of systemic rhIGF-1/rhIGFBP-3 to the preterm brain, and show that the interaction between systemic rhIGF-1/rhIGFBP-3 and choroid plexus varies over time.

Length-Dependent Translation Efficiency of ER-Destined Proteins.

Gene expression is a fundamental process that enables cells to produce specific proteins in a timely and spatially dependent manner. In eukaryotic cells, the complex organization of the cell body requires precise control of protein synthesis and localization. Certain mRNAs encode proteins with an N-terminal signal sequences that direct the translation apparatus toward a specific organelle. Here, we focus on the mechanisms governing the translation of mRNAs, which encode proteins with an endoplasmic reticulum (ER) signal in human cells. The binding of a signal-recognition particle (SRP) to the translation machinery halts protein synthesis until the mRNA-ribosome complex reaches the ER membrane. The commonly accepted model suggests that mRNA that encodes a protein that contains an ER signal peptide continuously repeats the cycle of SRP binding followed by association and dissociation with the ER. In contrast to the current view, we show that the long mRNAs remain on the ER while being translated. On the other hand, due to low ribosome occupancy, the short mRNAs continue the cycle, always facing a translation pause. Ultimately, this leads to a significant drop in the translation efficiency of small, ER-targeted proteins. The proposed mechanism advances our understanding of selective protein synthesis in eukaryotic cells and provides new avenues to enhance protein production in biotechnological settings.

Genetics, environmental stress, and amino acid supplementation affect lactational performance via mTOR signaling pathway in bovine mammary epithelial cells.

Mammary glands are known for their ability to convert nutrients present in the blood into milk contents. In cows, milk synthesis and the proliferation of cow mammary epithelial cells (CMECs) are regulated by various factors, including nutrients such as amino acids and glucose, hormones, and environmental stress. Amino acids, in particular, play a crucial role in regulating cell proliferation and casein synthesis in mammalian epithelial cells, apart from being building blocks for protein synthesis. Studies have shown that environmental factors, particularly heat stress, can negatively impact milk production performance in dairy cattle. The mammalian target of rapamycin complex 1 (mTORC1) pathway is considered the primary signaling pathway involved in regulating cell proliferation and milk protein and fat synthesis in cow mammary epithelial cells in response to amino acids and heat stress. Given the significant role played by the mTORC signaling pathway in milk synthesis and cell proliferation, this article briefly discusses the main regulatory genes, the impact of amino acids and heat stress on milk production performance, and the regulation of mTORC signaling pathway in cow mammary epithelial cells.

Plumbagin induces apoptosis, cell cycle arrest, and inhibits protein synthesis in LoVo colon cancer cells: A proteomic analysis.

Extracted from the roots of Plumbago zeylanica L., plumbagin is a natural naphthoquinone with potential as an anticancer compound. However, no studies have investigated its impact on LoVo (colon cancer) cells, and the specific mechanisms by which plumbagin exerts its anticancer effects remain to be established. The anticancer potential of plumbagin against LoVo cells was evaluated using a battery of assays, including MTT assay, clone formation assay, transwell chamber invasion assay, and wound-curing assay. Cell cycle analysis and cell apoptosis analysis were conducted to break down the anticancer impact of plumbagin on LoVo cells. A label-free proteomics technology was employed to investigate alterations in protein expression in LoVo cells treated with plumbagin. Our investigation indicated that plumbagin markedly inhibited the LoVo cells proliferation, and induced the apoptosis in LoVo cells, simultaneously induced G0/G1 phase cell cycle arrest. The LC-MS/MS proteomics assay revealed 78 proteins that were differentially expressed upon treatment with plumbagin. Bioinformatics and functional analyses indicated that these proteins were predominantly involved in protein synthesis and translation. Our findings revealed that multiple mechanisms are involved in the anticancer activity of plumbagin against LoVo cells, resulting in decreased cell viability. Proteomic analysis suggests that plumbagin may impede protein synthesis by reducing the expression of eukaryotic initiation factors. Our findings demonstrate that plumbagin exerts its anticancer activity against LoVo cells through multiple mechanisms, including inhibition of cell proliferation, induction of apoptosis, cell cycle arrest, and disruption of protein synthesis. These results provide new insights into the therapeutic potential of plumbagin for colon cancer treatment.

The structural basis of hyperpromiscuity in a core combinatorial network of type II toxin–antitoxin and related phage defense systems

Toxin-antitoxin (TA) systems are a large group of small genetic modules found in prokaryotes and their mobile genetic elements. Type II TAs are encoded as bicistronic (two-gene) operons that encode two proteins: a toxin and a neutralizing antitoxin. Using our tool NetFlax (standing for Network-FlaGs for toxins and antitoxins), we have performed a large-scale bioinformatic analysis of proteinaceous TAs, revealing interconnected clusters constituting a core network of TA-like gene pairs. To understand the structural basis of toxin neutralization by antitoxins, we have predicted the structures of 3,419 complexes with AlphaFold2. Together with mutagenesis and functional assays, our structural predictions provide insights into the neutralizing mechanism of the hyperpromiscuous Panacea antitoxin domain. In antitoxins composed of standalone Panacea, the domain mediates direct toxin neutralization, while in multidomain antitoxins the neutralization is mediated by other domains, such as PAD1, Phd-C, and ZFD. We hypothesize that Panacea acts as a sensor that regulates TA activation. We have experimentally validated 16 NetFlax TA systems and used domain annotations and metabolic labeling assays to predict their potential mechanisms of toxicity (such as membrane disruption, and inhibition of cell division or protein synthesis) as well as biological functions (such as antiphage defense). We have validated the antiphage activity of a RosmerTA system encoded by Gordonia phage Kita, and used fluorescence microscopy to confirm its predicted membrane-depolarizing activity. The interactive version of the NetFlax TA network that includes structural predictions can be accessed at http://netflax.webflags.se/.

Leukoencephalopathy with vanishing white matter disease: a case report study.

The authors report two cases of VWM disease. In the first case, an 8-month-old female child, brought to the pediatric clinic with seizure and loss of consciousness. The second case was a 24-month-old girl, presented with weakness, a disability to walk and swallow, and poor feeding. Her brain MRI demonstrated cystic changes (white matter rarefaction) in supratentorial peri-ventricular white matter and genetic testing result showed an EIF2B3 gene mutation. Leukoencephalopathy with VWM, also known as Cree encephalopathy is caused by mutations in the EIF2B gene. The disease is inherited in an autosomal recessive fashion. There are various agents leading to symptoms and signs of VWM disease. Physical stress like head trauma even in a mild degree, infections, and febrile diseases can be mentioned as causes of VWM. The eIF2B complex, plays a role as an important factor in the regulation of protein synthesis in cells under different conditions. As a conclusion, genetic counseling could be recommended to all individuals with VWM disease and their family members for next pregnancies and possible precautions for consanguineous marriages.

Cattle-compost-soil: The transfer of antibiotic resistance in livestock agriculture.

Antibiotic resistance is a major global health threat. Agricultural use of antibiotics is considered to be a main contributor to the issue, influencing both animals and humans as defined by the One Health approach. The purpose of the present study was to determine the abundance of antibiotic-resistant bacterial populations and the overall bacterial diversity of cattle farm soils that have been treated with animal manure compost. Soil and manure samples were collected from different sites at Tullimba farm, NSW. Cultures were grown from these samples in the presence of 11 commonly used antibiotics and antibiotic-resistant bacteria (ARB) colonies were identified. Soil and manure bacterial diversity was also determined using 16S ribosomal RNA next-generation sequencing. Results showed that ARB abundance was greatest in fresh manure and significantly lower in composted manure. However, the application of composted manure on paddock soil led to a significant increase in soil ARB abundance. Of the antibiotics tested, the number of ARB in each sample was greatest for antibiotics that inhibited the bacterial cell wall and protein synthesis. Collectively, these results suggest that the transfer of antibiotic resistance from composted animal manure to soil may not be solely mediated through the application of live bacteria and highlight the need for further research into the mechanism of antibiotic resistance transfer.

FoxM1 coordinates cell division, protein synthesis, and mitochondrial activity in a subset of β cells during acute metabolic stress

Pancreatic β cells display functional and transcriptional heterogeneity in health and disease. The sequence of events leading to β cell heterogeneity during metabolic stress is poorly understood. Here, we characterize β cell responses to early metabolic stress invivo by employing RNA sequencing (RNA-seq), assay for transposase-accessible chromatin with sequencing(ATAC-seq), single-cell RNA-seq (scRNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq), and real-time imaging to decipher temporal events of chromatin remodeling and gene expression regulating the unfolded protein response (UPR), protein synthesis, mitochondrial function, and cell-cycle progression. We demonstrate that a subpopulation of β cells with active UPR, decreased protein synthesis, and insulin secretary capacities is more susceptible to proliferation after insulin depletion. Alleviation of endoplasmic reticulum (ER) stress precedes the progression of the cell cycle and mitosis and ensures appropriate insulin synthesis. Furthermore, metabolic stress rapidly activates key transcription factors including FoxM1, which impacts on proliferative and quiescent β cells by regulating protein synthesis, ER stress, and mitochondrial activity via direct repression of mitochondrial-encoded genes.

A Review on the Involvement of Heat Shock Proteins (Extrinsic Chaperones) in Response to Stress Conditions in Aquatic Organisms.

Heat shock proteins (HSPs) encompass both extrinsic chaperones and stress proteins. These proteins, with molecular weights ranging from 14 to 120 kDa, are conserved across all living organisms and are expressed in response to stress. The upregulation of specific genes triggers the synthesis of HSPs, facilitated by the interaction between heat shock factors and gene promoter regions. Notably, HSPs function as chaperones or helper molecules in various cellular processes involving lipids and proteins, and their upregulation is not limited to heat-induced stress but also occurs in response to anoxia, acidosis, hypoxia, toxins, ischemia, protein breakdown, and microbial infection. HSPs play a vital role in regulating protein synthesis in cells. They assist in the folding and assembly of other cellular proteins, primarily through HSP families such as HSP70 and HSP90. Additionally, the process of the folding, translocation, and aggregation of proteins is governed by the dynamic partitioning facilitated by HSPs throughout the cell. Beyond their involvement in protein metabolism, HSPs also exert a significant influence on apoptosis, the immune system, and various characteristics of inflammation. The immunity of aquatic organisms, including shrimp, fish, and shellfish, relies heavily on the development of inflammation, as well as non-specific and specific immune responses to viral and bacterial infections. Recent advancements in aquatic research have demonstrated that the HSP levels in populations of fish, shrimp, and shellfish can be increased through non-traumatic means such as water or oral administration of HSP stimulants, exogenous HSPs, and heat induction. These methods have proven useful in reducing physical stress and trauma, while also facilitating sustainable husbandry practices such as vaccination and transportation, thereby offering health benefits. Hence, the present review discusses the importance of HSPs in different tissues in aquatic organisms (fish, shrimp), and their expression levels during pathogen invasion; this gives new insights into the significance of HSPs in invertebrates.

Metamorphic gene regulation programs in Xenopus tropicalis tadpole brain.

Amphibian metamorphosis is controlled by thyroid hormone (TH), which binds TH receptors (TRs) to regulate gene expression programs that underlie morphogenesis. Gene expression screens using tissues from premetamorphic tadpoles treated with TH identified some TH target genes, but few studies have analyzed genome-wide changes in gene regulation during spontaneous metamorphosis. We analyzed RNA sequencing data at four developmental stages from the beginning to the end of spontaneous metamorphosis, conducted on the neuroendocrine centers of Xenopus tropicalis tadpole brain. We also conducted chromatin immunoprecipitation sequencing (ChIP-seq) for TRs, and we compared gene expression changes during metamorphosis with those induced by exogenous TH. The mRNA levels of 26% of protein coding genes changed during metamorphosis; about half were upregulated and half downregulated. Twenty four percent of genes whose mRNA levels changed during metamorphosis had TR ChIP-seq peaks. Genes involved with neural cell differentiation, cell physiology, synaptogenesis and cell-cell signaling were upregulated, while genes involved with cell cycle, protein synthesis, and neural stem/progenitor cell homeostasis were downregulated. There is a shift from building neural structures early in the metamorphic process, to the differentiation and maturation of neural cells and neural signaling pathways characteristic of the adult frog brain. Only half of the genes modulated by treatment of premetamorphic tadpoles with TH for 16 h changed expression during metamorphosis; these represented 33% of the genes whose mRNA levels changed during metamorphosis. Taken together, our results provide a foundation for understanding the molecular basis for metamorphosis of tadpole brain, and they highlight potential caveats for interpreting gene regulation changes in premetamorphic tadpoles induced by exogenous TH.

Characterization of the biochemical activity and tumor-promoting role of the dual protein methyltransferase METL-13/METTL13 in Caenorhabditis elegans.

The methyltransferase-like protein 13 (METTL13) methylates the eukaryotic elongation factor 1 alpha (eEF1A) on two locations: the N-terminal amino group and lysine 55. The absence of this methylation leads to reduced protein synthesis and cell proliferation in human cancer cells. Previous studies showed that METTL13 is dispensable in non-transformed cells, making it potentially interesting for cancer therapy. However, METTL13 has not been examined yet in whole animals. Here, we used the nematode Caenorhabditis elegans as a simple model to assess the functions of METTL13. Using methyltransferase assays and mass spectrometry, we show that the C. elegans METTL13 (METL-13) methylates eEF1A (EEF-1A) in the same way as the human protein. Crucially, the cancer-promoting role of METL-13 is also conserved and depends on the methylation of EEF-1A, like in human cells. At the same time, METL-13 appears dispensable for animal growth, development, and stress responses. This makes C. elegans a convenient whole-animal model for studying METL13-dependent carcinogenesis without the complications of interfering with essential wild-type functions.