Two new species of Fusarium in the F. incarnatum-equiseti species complex from Oryza sativa in Iran.

Identification of Fusarium species associated with diseases symptoms in plants is an important step toward understanding the ecology of plant-fungus associations. In this study, four Fusarium isolates were obtained from root rot of Oryza sativa L. in Izeh (southwest of Iran) and identified based on phylogenetic analyses combined with morphology. Phylogenetic analyses based on combined translation elongation factor 1-α, calmodulin, RNA polymerase II second largest subunit, and Beta-tubulin (tub2) sequence data delimited two new species, namely F. khuzestanicum and F. oryzicola spp. nov., from previously known species of Fusarium within F. incarnatum-equiseti species complex (FIESC). Morphologically, F. khuzestanicum produces the macroconidia with distinctly notched to foot-shaped basal cells, while basal cells in the macroconidia of F. oryzicola are more extended and distinctly elongated foot shape. Furthermore, these two new species are distinguished by the size of their sporodochial phialides and macroconidia. The results of the present show that the FIESC species complex represent more cryptic species.

Identification of hub genes and potential networks by centrality network analysis of PCR amplified Fusarium oxysporum f. sp. lycopersici EF1α gene.

BACKGROUND: Fusarium wilt is a devastating soil-borne fungal disease of tomato across the world. Conventional method of disease prevention including usage of common pesticides and methods like soil solarisation are usually ineffective in the treatment of this disease. Therefore, there is an urgent need to identify virulence related genes in the pathogen which can be targeted for fungicide development. RESULTS: Pathogenicity testing and phylogenetic classification of the pathogen used in this study confirmed it as Fusarium oxysporum f. sp. lycopersici (Fol) strain. A recent discovery indicates that EF1α, a protein with conserved structural similarity across several fungal genera, has a role in the pathogenicity of Magnaporthe oryzae, the rice blast fungus. Therefore, in this study we have done structural and functional classification of EF1α to understand its role in pathogenicity of Fol. The protein model of Fol EF1α was created using the template crystal structure of the yeast elongation factor complex EEF1A:EEF1BA which showed maximum similarity with the target protein. Using the STRING online database, the interactive information among the hub genes of EF1α was identified and the protein-protein interaction network was recognized using the Cytoscape software. On combining the results of functional analysis, MCODE, CytoNCA and CytoHubba 4 hub genes including Fol EF1α were selected for further investigation. The three interactors of Fol EF1α showed maximum similarity with homologous proteins found in Neurospora crassa complexed with the known fungicide, cycloheximide. Through the sequence similarity and PDB database analysis, homologs of Fol EF1α were found: EEF1A:EEF1BA in complex with GDPNP in yeast and EF1α in complex with GDP in Sulfolobus solfataricus. The STITCH database analysis suggested that EF1α and its other interacting partners interact with guanosine diphosphate (GDPNP) and guanosine triphosphate (GTP). CONCLUSIONS: Our study offers a framework for recognition of several hub genes network in Fusarium wilt that can be used as novel targets for fungicide development. The involvement of EF1α in nucleocytoplasmic transport pathway suggests that it plays role in GTP binding and thus apart from its use as a biomarker, it may be further exploited as an effective target for fungicide development. Since, the three other proteins that were found to be tightly associated Fol EF1α have shown maximum similarity with homologous proteins of Neurospora crassa that form complex with fungicide- Cycloheximide. Therefore, we suggest that cycloheximide can also be used against Fusarium wilt disease in tomato. The active site cavity of Fol EF1α can also be determined for computational screening of fungicides using the homologous proteins observed in yeast and Sulfolobus solfataricus. On this basis, we also suggest that the other closely associated genes that have been identified through STITCH analysis, they can also be targeted for fungicide development.

Ac4C modification of lncRNA SIMALR promotes nasopharyngeal carcinoma progression through activating eEF1A2 to facilitate ITGB4/ITGA6 translation.

The dysregulation of long non-coding RNAs (lncRNAs) are involved in regulating tumor progression in multiple manner. However, little is known about whether lncRNA is involved in the translation regulation of proteins. Here, we identified that the suppressor of inflammatory macrophage apoptosis lncRNA (SIMALR) was highly expressed in nasopharyngeal carcinoma (NPC) tissues by analyzing the lncRNA microarray. Clinically, the high expression of SIMALR served as an independent predictor for inferior prognosis in NPC patients. SIMALR functioned as an oncogenic lncRNA that promoted the proliferation and metastasis of NPC cells in vitro and in vivo. Mechanistically, SIMALR served as a critical accelerator of protein synthesis by binding to eEF1A2 (eukaryotic translation elongation factor 1 alpha 2), one of the most crucial regulators in the translation machinery of the eukaryotic cells, and enhancing its endogenous GTPase activity. Furthermore, SIMALR mediated the activation of eEF1A2 phosphorylation to accelerate the translation of ITGB4/ITGA6, ultimately promoting the malignant phenotype of NPC cells. In addition, N-acetyltransferase 10 (NAT10) enhanced the stability of SIMALR and caused its overexpression in NPC through the N4-acetylcytidine (ac4C) modification. In sum, our results illustrate SIMALR functions as an accelerator for protein translation and highlight the oncogenic role of NAT10-SIMALR-eEF1A2-ITGB4/6 axis in NPC.

eEF1α2 is required for actin cytoskeleton homeostasis in the aging muscle.

The translation elongation factor eEF1α (eukaryotic elongation factor 1α) mediates mRNA translation by delivering aminoacyl-tRNAs to ribosomes. eEF1α also has other reported roles, including the regulation of actin dynamics. However, these distinct roles of eEF1α are often challenging to uncouple and remain poorly understood in aging metazoan tissues. The genomes of mammals and Drosophila encode two eEF1α paralogs, with eEF1α1 expressed ubiquitously and eEF1α2 expression more limited to neurons and muscle cells. Here, we report that eEF1α2 plays a unique role in maintaining myofibril homeostasis during aging in Drosophila. Specifically, we generated an eEF1α2 null allele, which was viable and showed two distinct muscle phenotypes. In young flies, the mutants had thinner myofibrils in indirect flight muscles that could be rescued by expressing eEF1α1. With aging, the muscles of the mutant flies began showing abnormal distribution of actin and myosin in muscles, but without a change in actin and myosin protein levels. This age-related phenotype could not be rescued by eEF1α1 overexpression. These findings support an unconventional role of Drosophila eEF1α2 in age-related homeostasis of muscle myofibers.

[Developmental and epileptic encephalopathy 33 caused by EEF1A2 gene mutation: a case report]. / EEF1A2åŸºå› å˜å¼‚è‡´å‘è‚²æ€§ç™«ç—«æ€§è„‘ç— 33型1例.

A boy, aged 7 months, presented with severe global developmental delay (GDD), refractory epilepsy, hypotonia, nystagmus, ocular hypertelorism, a broad nasal bridge, everted upper lip, a high palatal arch, and cryptorchidism. Genetic testing revealed a de novo heterozygous missense mutation of c.364G>A(p.E122K) in the EEF1A2 gene, and finally the boy was diagnosed with autosomal dominant developmental and epileptic encephalopathy 33 caused by the EEF1A2 gene mutation. This case report suggests that for children with unexplained infancy-onset severe to profound GDD/intellectual disability and refractory epilepsy, genetic testing for EEF1A2 gene mutations should be considered. This is particularly important for those exhibiting hypotonia, nonverbal communication, and craniofacial deformities, to facilitate a confirmed diagnosis.

A description of two novel Psilocybe species from southern Africa and some notes on African traditional hallucinogenic mushroom use.

Two new Psilocybe species (Hymenogastraceae), P. ingeli and P. maluti, are described from southern Africa. Morphology and phylogeny were used to separate the two novel fungi from their closest relatives in the genus. Psilocybe ingeli was found fruiting on bovine manure-enriched grasslands in the Kwa-Zulu Natal Province of South Africa and differs from its closest relative P. keralensis and others in the internal transcribed spacer ITS1-5.8S-ITS2, partial 28S nuc rDNA, and translation elongation factor 1-alpha regions, distribution, and having larger basidiospores. Similarly, P. maluti was collected from the Free State Province of South Africa and observed in the Kingdom of Lesotho, growing on bovine manure. A secotioid pileus, geographic distribution, and differences in the same DNA regions distinguish P. maluti from its closest relative P. chuxiongensis. Furthermore, the spore dispersal and traditional, spiritualistic use of P. maluti are discussed here.

UCHL3 promotes hepatocellular carcinoma progression by stabilizing EEF1A1 through deubiquitination.

BACKGROUND: Hepatocellular carcinoma (HCC) ranks as the second leading cause of global cancer-related deaths and is characterized by a poor prognosis. Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) have been proved to play important roles in various human cancers, whereas the deubiquitination of EEF1A1 was poorly understood. METHODS: The binding and regulatory relationship between Ubiquitin carboxyl-terminal hydrolase L3 (UCHL3) and EEF1A1 was validated using clinical tissue samples, reverse transcription quantitative real-time fluorescence quantitative PCR (RT-qPCR), Western blotting, co-immunoprecipitation, and immunofluorescence, as well as ubiquitin detection and cyclohexamide tracking experiments. Finally, the impact of the UCHL3/EEF1A1 axis on HCC malignant behavior was analyzed through functional experiments and nude mouse models. RESULTS: UCHL3 was found to have a high expression level in HCC tissues. Tissue samples from 60 HCC patients were used to evaluate the correlation between UCHL3 and EEF1A1. UCHL3 binds to EEF1A1 through the lysine site, which reduces the ubiquitination level of EEF1A1. Functional experiments and nude mouse models have demonstrated that the UCHL3/EEF1A1 axis promotes the migration, stemness, and drug resistance of HCC cells. Reducing the expression of EEF1A1 can reverse the effect of UCHL3 on the malignant behavior of HCC cells. CONCLUSION: Our findings revealed that UCHL3 binds and stabilizes EEF1A1 through deubiquitination. UCHL3 and EEF1A1 formed a functional axis in facilitating the malignant progression of HCC, proving new insights for the anti-tumor targeted therapy for HCC.

Synthesis and biological evaluation of vioprolide B and its dehydrobutyrine-glycine analogue.

Herein, we describe the total synthesis of the depsipeptide vioprolide B and of an analogue, in which the (E)-dehydrobutyrine amino acid was replaced by glycine. The compounds were studied in biological assays which revealed cytotoxicity solely for vioprolide B presumably by covalent binding to cysteine residues of elongation factor eEF1A1 and of chromatin assembly factor CHAF1A.

Morphological and phylogenetic analyses reveal four species of myxomycetes new to China.

Four species of myxomycetes (Arcyria pseudodenudata, Diderma europaeum, Lycogala irregulare, and Trichia armillata) new to China were observed via light microscope and scanning electron microscope, and detailed descriptions and illustrations are provided, along with comparisons with related species. Among them, A. pseudodenudata was discovered for the first time outside of the type locality, D. europaeum was discovered for the first time outside of Europe, and L. irregulare and T. armillata were reported again after being named. Phylogenetic analyses based on nuclear 18S rDNA and elongation factor-1 alpha sequences or nuclear 18S rDNA and cytochrome oxidase subunit I sequences was performed to provide a molecular basis for morphological identification. These specimens were deposited in the Herbarium of Fungi of Nanjing Normal University.

Perturbation of METTL1-mediated tRNA N7- methylguanosine modification induces senescence and aging.

Cellular senescence is characterized by a decrease in protein synthesis, although the underlying processes are mostly unclear. Chemical modifications to transfer RNAs (tRNAs) frequently influence tRNA activity, which is crucial for translation. We describe how tRNA N7-methylguanosine (m7G46) methylation, catalyzed by METTL1-WDR4, regulates translation and influences senescence phenotypes. Mettl1/Wdr4 and m7G gradually diminish with senescence and aging. A decrease in METTL1 causes a reduction in tRNAs, especially those with the m7G modification, via the rapid tRNA degradation (RTD) pathway. The decreases cause ribosomes to stall at certain codons, impeding the translation of mRNA that is essential in pathways such as Wnt signaling and ribosome biogenesis. Furthermore, chronic ribosome stalling stimulates the ribotoxic and integrative stress responses, which induce senescence-associated secretory phenotype. Moreover, restoring eEF1A protein mitigates senescence phenotypes caused by METTL1 deficiency by reducing RTD. Our findings demonstrate that tRNA m7G modification is essential for preventing premature senescence and aging by enabling efficient mRNA translation.

EEF1B2 regulates bone marrow-derived mesenchymal stem cells bone-fat balance via Wnt/ß-catenin signaling.

The pathological advancement of osteoporosis is caused by the uneven development of bone marrow-derived mesenchymal stem cells (BMSCs) in terms of osteogenesis and adipogenesis. While the role of EEF1B2 in intellectual disability and tumorigenesis is well established, its function in the bone-fat switch of BMSCs is still largely unexplored. During the process of osteogenic differentiation, we observed an increase in the expression of EEF1B2, while a decrease in its expression was noted during adipogenesis. Suppression of EEF1B2 hindered the process of osteogenic differentiation and mineralization while promoting adipogenic differentiation. On the contrary, overexpression of EEF1B2 enhanced osteogenesis and strongly inhibited adipogenesis. Furthermore, the excessive expression of EEF1B2 in the tibias has the potential to mitigate bone loss and decrease marrow adiposity in mice with osteoporosis. In terms of mechanism, the suppression of ß-catenin activity occurred when EEF1B2 function was suppressed during osteogenesis. Our collective findings indicate that EEF1B2 functions as a regulator, influencing the differentiation of BMSCs and maintaining a balance between bone and fat. Our finding highlights its potential as a therapeutic target for diseases related to bone metabolism.

High expression of eukaryotic elongation factor 1-alpha-2 in lung adenocarcinoma is associated with poor prognosis.

Eukaryotic elongation factor 1 alpha 2 (eEF1A2) encodes an isoform of the alpha subunit of the elongation factor 1 complex and is responsible for the enzymatic delivery of aminoacyl tRNA to the ribosome. Our proteomic analysis has identified eEF1A2 as one of the proteins expressed during malignant progression from adenocarcinoma in situ (AIS) to early invasive lung adenocarcinoma. The expression level of eEF1A2 in 175 lung adenocarcinomas was examined by immunohistochemical staining in relation to patient prognosis and clinicopathological factors. Quantitative PCR analysis and fluorescence in situ hybridization (FISH) were performed to evaluate the amplification of the eEF1A2 gene. Relatively high expression of eEF1A2 was observed in invasive adenocarcinoma (39/144 cases) relative to minimally invasive adenocarcinoma (1/10 cases) or AIS (0/21 cases). Among invasive adenocarcinomas, solid-type adenocarcinoma (15/32 cases, 47%) showed higher expression than other histological subtypes (23/92, 25%). Patients with eEF1A2-positive tumors had a significantly poorer prognosis than those with eEF1A2-negative tumors. Of the five tumors that were eEF1A2-positive, two cases showed amplified genomic eEF1A2 DNA, which was confirmed by both qPCR and FISH. These findings indicate that eEF1A2 overexpression occurs in the course of malignant transformation of lung adenocarcinomas and is partly due to eEF1A2 gene amplification.

Ophiostoma haidaense, sp. nov., a new member of the O. piceae species complex associated with yellow-cedar, Callitropsis nootkatensis.

Ophiostoma haidanensis is described as a new species of the Ophiostoma piceae complex isolated from yellow-cedar (Callitropsis nootkatensis (D. Don) Oerst. ex D.P. Little) sapwood in the Haida Gwaii island archipelago and the North Coast of British Columbia, Canada. The fungus is characterized by the production of a typical sporothrix-like asexual morph but is distinguished morphologically from other members of the O. piceae species complex by its large, multiseptate primary conidia. Phylogenetic analysis of DNA sequences from the nuc rDNA internal transcribed spacer region ITS1-5.8S-ITS2 (ITS) and the ß-tubulin (BTUB) and translation elongation factor 1-α (TEF1) genes supports the inclusion of O. haidensis as a distinct member within the O. piceae complex. To our knowledge, this is the first report of a blue stain fungus infecting yellow-cedar, an ecologically, culturally, and economically important conifer naturally distributed along the coastal forests of the Pacific Northwest in North America.

Downfall of an empire: Unmasking the hidden diversity and distribution of the Amanita rubescens species complex.

Amanita is one of the most salient mushroom genera due to its cultural, economic, and medical importance. Recently, many new Amanita species have been described worldwide, increasing the genus richness. However, several clades have cryptic diversity, and many species complexes have not yet been resolved. This is the case of the rubescent species in the Validae section, which have been widely cited under the name Amanita rubescens s.l. We used a four-locus matrix (nuc rDNA internal transcribed spacer [ITS] and 28S regions and genes for RNA polymerase II subunit 2 [rpb2], translation elongation factor 1-α [tef1-α], and ß-tubulin [tub2]) to solve the phylogenetic relationships within the Amanita section Validae. To analyze the diversity and distribution patterns of species, we used an extensive ITS sequence sampling including environmental DNA databases. The phylogenetic analyses demonstrated that the Validae section is divided into three monophyletic and highly supported major clades: Mappae, Validae, and Rubescentes. At least 11 species-level clades within the Rubescentes clade were highly supported: A. cruentilemurum nom. prov. A. brunneolocularis, A. rubescens s.s. (European clade), A. rubescens s.s. (Asiatic clade), A. orsonii s.s. A. 'orsonii,' A. aureosubucula nom. prov., A. novinupta, A. flavorubens, and two undescribed North American species. We proved that A. rubescens s.s. has two segregated populations (European and Asiatic) and it is not naturally distributed in America. Furthermore, we found that America has more cryptic species within the Rubescentes clade than Eurasia.

Discovery of Botryosphaeria eucalypti sp. nov. from blighted Eucalyptus leaves in India.

Eucalyptus spp. are undoubtedly one of the most favored plantation trees globally. Accurately identifying Eucalyptus pathogens is therefore crucial for timely disease prevention and control. Recently, symptoms of a leaf blight disease were observed on Eucalyptus trees in plantations at Jhajjar and Karnal in the state of Haryana, northern India. Asexual morphs resembling the features of the Botryosphaeriaceae were consistently isolated from the symptomatic leaves. Morphological features coupled with DNA sequence analysis confirmed a novel species, which is described and illustrated here as Botryosphaeria eucalypti sp. nov. Conidia of the new taxon are longer and wider than those of its phylogenetic neighbors. A distinct phylogenetic position for the new taxon was established through combined analysis of the internal transcribed spacer (ITS), partial translation elongation factor-1α (tef1) and partial ß-tubulin (tub2) regions. Recombination analysis provided additional support for the new species hypothesis. The pathogenicity of the novel species was proved on Eucalyptus leaves, and Koch's postulates were fulfilled. The discovery of new Botryosphaeria species is important because it will help in understanding the species diversity, host range, possible threats and disease control in the long run.

FBXO32 Stimulates Protein Synthesis to Drive Pancreatic Cancer Progression and Metastasis.

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death worldwide, primarily due to its rapid progression. The current treatment options for PDAC are limited, and a better understanding of the underlying mechanisms responsible for PDAC progression is required to identify improved therapeutic strategies. In this study, we identified FBXO32 as an oncogenic driver in PDAC. FBXO32 was aberrantly upregulated in PDAC, and high FBXO32 expression was significantly associated with an unfavorable prognosis in patients with PDAC. FRG1 deficiency promoted FBXO32 upregulation in PDAC. FBXO32 promoted cell migration and invasion in vitro and tumor growth and metastasis in vivo. Mechanistically, FBXO32 directly interacted with eEF1A1 and promoted its polyubiquitination at the K273 site, leading to enhanced activity of eEF1A1 and increased protein synthesis in PDAC cells. Moreover, FBXO32-catalyzed eEF1A1 ubiquitination boosted the translation of ITGB5 mRNA and activated focal adhesion kinase (FAK) signaling, thereby facilitating focal adhesion assembly and driving PDAC progression. Importantly, interfering with the FBXO32-eEF1A1 axis or pharmaceutical inhibition of FAK by defactinib, an FDA-approved FAK inhibitor, substantially inhibited PDAC growth and metastasis driven by aberrantly activated FBXO32-eEF1A1 signaling. Overall, this study uncovers a mechanism by which PDAC cells rely on FBXO32-mediated eEF1A1 activation to drive progression and metastasis. FBXO32 may serve as a promising biomarker for selecting eligible patients with PDAC for treatment with defactinib. Significance: FBXO32 upregulation in pancreatic cancer induced by FRG1 deficiency increases eEF1A1 activity to promote ITGB5 translation and stimulate FAK signaling, driving cancer progression and sensitizing tumors to the FAK inhibitor defactinib.

EEF1D stabilized by SRSF9 promotes colorectal cancer via enhancing the proliferation and metastasis.

Colorectal cancer (CRC) is the third most common cancer and causes high mortality worldwide. Although CRC has been studied widely, the molecular mechanism is not completely known. Eukaryotic translation elongation factor 1 delta (EEF1D) participates in the progression of various tumors, however, the effect of EEF1D on CRC remains unclear. Here, we aimed to identify the potential mechanism of EEF1D in CRC. The expression levels of EEF1D were assessed in CRC samples. Functional analysis of EEF1D in CRC was detected in vitro and in vivo. The regulatory mechanism of EEF1D was identified with RNA immunoprecipitation, RNA pull-down assay, and proteomics analysis. Our findings confirmed that EEF1D was upregulated in human CRC tissues. Functionally, EEF1D overexpression accelerated cell proliferation and metastasis, whereas EEF1D knockdown inhibited cell proliferation and metastasis both in vitro and in vivo CRC models. Furthermore, we showed that EEF1D was upregulated by SRSF9 via binding to 3'UTR of EEF1D mRNA. EEF1D knockdown reversed the malignant phenotype induced by SRSF9 overexpression. These findings demonstrated that EEF1D promotes CRC progression, and EEF1D may be a molecular target against CRC.

CRISPR Screen Identifies the RNA-Binding Protein Eef1a1 as a Key Regulator of Myogenesis.

Skeletal muscle myogenesis hinges on gene regulation, meticulously orchestrated by molecular mechanisms. While the roles of transcription factors and non-coding RNAs in myogenesis are widely known, the contribution of RNA-binding proteins (RBPs) has remained unclear until now. Therefore, to investigate the functions of post-transcriptional regulators in myogenesis and uncover new functional RBPs regulating myogenesis, we employed CRISPR high-throughput RBP-KO (RBP-wide knockout) library screening. Through this approach, we successfully identified Eef1a1 as a novel regulatory factor in myogenesis. Using CRISPR knockout (CRISPRko) and CRISPR interference (CRISPRi) technologies, we successfully established cellular models for both CRISPRko and CRISPRi. Our findings demonstrated that Eef1a1 plays a crucial role in promoting proliferation in C2C12 myoblasts. Through siRNA inhibition and overexpression methods, we further elucidated the involvement of Eef1a1 in promoting proliferation and suppressing differentiation processes. RIP (RNA immunoprecipitation), miRNA pull-down, and Dual-luciferase reporter assays confirmed that miR-133a-3p targets Eef1a1. Co-transfection experiments indicated that miR-133a-3p can rescue the effect of Eef1a1 on C2C12 myoblasts. In summary, our study utilized CRISPR library high-throughput screening to unveil a novel RBP, Eef1a1, involved in regulating myogenesis. Eef1a1 promotes the proliferation of myoblasts while inhibiting the differentiation process. Additionally, it acts as an antagonist to miR-133a-3p, thus modulating the process of myogenesis.

The elongation factor 1-alpha as storage reserve and environmental sensor in Nicotiana tabacum L. seeds.

Given their critical role in plant reproduction and survival, seeds demand meticulous regulatory mechanisms to effectively store and mobilize reserves. Within seeds, the condition of storage reserves heavily depends on environmental stimuli and hormonal activation. Unlike non-protein reserves that commonly employ dedicated regulatory proteins for signaling, proteinaceous reserves may show a unique form of 'self-regulation', amplifying efficiency and precision in this process. Proteins rely on stability to carry out their functions. However, in specific physiological contexts, particularly in seed germination, protein instability becomes essential, fulfilling roles from signaling to regulation. In this study, the elongation factor 1-alpha has been identified as a main proteinaceous reserve in Nicotiana tabacum L. seeds and showed peculiar changes in stability based on tested chemical and physical conditions. A detailed biochemical analysis followed these steps to enhance our understanding of these protein attributes. The protein varied its behavior under different conditions of pH, temperature, and salt concentration, exhibiting shifts within physiological ranges. Notably, distinct solubility transitions were observed, with the elongation factor 1-alpha becoming insoluble upon reaching specific thresholds determined by the tested chemical and physical conditions. The findings are discussed within the context of seed signaling in response to environmental conditions during the key transitions of dormancy and germination.

eEF1A1 regulates the expression and alternative splicing of genes associated with Parkinson's disease in U251 cells.

BACKGROUND: Eukaryotic elongation factor 1A1 (eEF1A1) is an RNA-binding protein that is associated with PARK2 activity in cells, suggesting a possible role in Parkinson's disease (PD). OBJECTIVE: To clear whether eEF1A1 plays a role in PD through transcriptional or posttranscriptional regulation. METHODS: The GSE68719 dataset was downloaded from the GEO database, and the RNA-seq data of all brain tissue autopsies were obtained from 29 PD patients and 44 neurologically normal control subjects. To inhibit eEF1A1 from being expressed in U251 cells, siRNA was transfected into those cells, and RNA-seq high-throughput sequencing was used to determine the differentially expressed genes (DEGs) and differentially alternative splicing events (ASEs) resulting from eEF1A1 knockdown. RESULTS: eEF1A1 was significantly overexpressed in PD brain tissue in the BA9 area. GO and KEGG enrichment analyses revealed that eEF1A1 knockdown significantly upregulated the expression of the genes CXCL10, NGF, PTX3, IL6, ST6GALNAC3, NUPR1, TNFRSF21, and CXCL2 and upregulated the alternative splicing of the genes ACOT7, DDX10, SHMT2, MYEF2, and NDUFAF5. These genes were enriched in pathways related to PD pathogenesis, such as apoptosis, inflammatory response, and mitochondrial dysfunction. CONCLUSION: The results suggesting that eEF1A1 involved in the development of PD by regulating the differential expression and alternative splicing of genes, providing a theoretical basis for subsequent research.