Ask about this productRelated genes to: ELAVL4 antibody
- Gene:
- ELAVL4 NIH gene
- Name:
- ELAV like RNA binding protein 4
- Previous symbol:
- HUD
- Synonyms:
- PNEM
- Chromosome:
- 1p33-p32.3
- Locus Type:
- gene with protein product
- Date approved:
- 1993-07-12
- Date modifiied:
- 2018-02-13
Related products to: ELAVL4 antibody
Related articles to: ELAVL4 antibody
- This study aimed to investigate the molecular mechanisms underlying dopaminergic injury induced by gestational and lactational atrazine (ATR) exposure in rat offspring, with a particular focus on non-coding RNA-mediated regulation. Pregnant rats were exposed to ATR during gestation and lactation. Offspring underwent behavioral testing at postnatal day 21 (PND21) and were sacrificed for midbrain tissue collection at PND28. Behavioral alterations, histopathological changes in the substantia nigra, and dopaminergic marker expression were assessed to evaluate ATR-induced neurotoxicity. Whole-transcriptome sequencing was then performed to identify differentially expressed mRNAs, miRNAs, and lncRNAs, followed by co-expression, protein-protein interaction, and competing endogenous RNA (ceRNA) network analyses. Key targets were validated by qRT-PCR. Candidate molecules identified from transcriptomic and ceRNA analyses were further examined in an ATR-induced neurotoxicity model established in RA-differentiated cells. Dual-luciferase reporter, Ago2-RNA immunoprecipitation, and biotin-labeled RNA pull-down assays were used to examine putative binding relationships and molecular interactions. In addition, lentivirus-mediated overexpression was performed to further evaluate the role of this candidate regulator in ATR-induced Nurr1 downregulation. Gestational and lactational ATR exposure induced significant behavioral abnormalities in rat offspring. These changes were accompanied by histopathological alterations in the substantia nigra, including reduced immunoreactivity, as well as abnormal expression of dopaminergic markers, characterized by decreased and levels and increased α-syn expression. Together, these findings indicate the presence of dopaminergic injury. Whole-transcriptome analysis further revealed widespread dysregulation of mRNAs, miRNAs, and lncRNAs in ATR-exposed offspring. Subsequent integrative analysis suggested a potential ceRNA regulatory relationship among , , and , which was further supported by qRT-PCR. Dual-luciferase reporter, RIP, and RNA pull-down assays supported direct interactions between and both and , as well as their association with the Ago2-containing silencing complex. Moreover, Elavl4 overexpression partially reversed ATR-induced Nurr1 downregulation in vitro. Gestational and lactational ATR exposure induced behavioral abnormalities and dopaminergic injury in rat offspring. Whole-transcriptome analysis combined with experimental validation suggests a potential association between the ceRNA axis and ATR-induced dopaminergic injury, providing insight into the post-transcriptional mechanisms underlying developmental neurotoxicity. - Source: PubMed
Publication date: 2026/04/25
Ma YongjieSun TianaoPan MinglianZheng ZhanyueWei JingxiaYuan XinyuWan JinhaoZhou YingjieSun Yan - Epstein-Barr virus (EBV), an oncogenic virus, actively remodels the intracellular environment during its lytic (replicative/productive) phase to facilitate genome replication, virion packaging, and egress while attempting to evade immune responses. A key aspect of this remodeling is the downregulation of host gene expression, a phenomenon known as host shutoff. This process is prominently mediated by the EBV-encoded nuclease BGLF5, but BGLF5-independent mechanisms also contribute - most notably, the viral lytic switch protein ZEBRA, which can suppress host protein synthesis. Despite this broad suppression, the expression of certain host genes essential for lytic progression must be preserved or even enhanced. To investigate how such genes evade host shutoff, we analyzed the expression of a set of cellular transcripts in Burkitt lymphoma cells, sorted 24 hours after exposure to lytic triggers, into lytic and refractory (non-lytic) populations. We identified a subset of host transcripts consistently upregulated in lytic cells across Burkitt lymphoma lines reactivated by functionally distinct lytic stimuli, indicating that such upregulation is independent of pleiotropic lytic cycle inducing stimuli. Importantly, we found that while ZEBRA suppresses protein expression of some of these host (and select viral) genes, it also transcriptionally upregulates two related host genes, ELAVL4 and PABPC4L. Both encode RNA-binding proteins, and we found that they differentially modulate viral transcript abundance - enhancing some while repressing others - ultimately supporting the transcriptional demands, efficient genome replication and virion release during the EBV lytic cycle. These findings highlight the virus's finely tuned regulation of both host and viral gene expression to ensure successful completion of the lytic cycle. Specifically, they suggest that EBV selectively upregulates critical host genes to counteract/escape host shutoff and promote virus propagation. - Source: PubMed
Publication date: 2026/05/11
Daigle DerekCreasy-Marrazzo AshtonGradoville LynEl-Guindy AymanMukherjee RishabhDas SandeepanBaral BudhadevRousseau Beth APark RichardMcIntosh Michael TMiller GeorgeBhaduri-McIntosh Sumita - Metabolic stress caused by lipid overload is a key driver of cellular dysfunction in aging and disease. Excess saturated fatty acids such as palmitate impair fatty acid oxidation (FAO), promote lipid accumulation, and increase reactive oxygen species (ROS), ultimately triggering premature senescence-like states. Senescence further amplifies vulnerability by worsening mitochondrial dysfunction, enhancing lipid imbalance, and sustaining pro-inflammatory signaling. Here, we investigated the role of the neuron-enriched RNA-binding protein HuD (ELAVL4) in protecting cells against lipotoxic stress. Using Neuro2a neuroblastoma cells, we found that HuD knockdown suppressed FAO, leading to increased lipid accumulation and elevated ROS following palmitate exposure. HuD-deficient cells also exhibited cytosolic mitochondrial DNA release, IRF phosphorylation, and upregulation of senescence markers. Mechanistically, RNA immunoprecipitation revealed that HuD binds directly to PPARα mRNA, sustaining its expression by competing with the PPARα-targeting microRNAs miR-9-5p and miR-22-3p. Loss of HuD reduced PPARα levels, thereby weakening the FAO capacity and sensitizing cells to palmitate-induced lipotoxic stress. These findings identify a previously unrecognized HuD-PPARα-FAO axis that restrains metabolic stress and senescence. By linking post-transcriptional regulation to lipid metabolism and inflammatory signaling, this work highlights stress-induced premature senescence as both an outcome and a propagator of metabolic dysfunction, providing insight into mechanisms of aging-related vulnerability. - Source: PubMed
Publication date: 2026/02/07
Ryu SeungyeonSeo JiyoonSim Ye EunJung Se HoonZhang WeiJeong Seung MinLee Eun Kyung - We investigated HuD (ELAVL4), a neuronal RNA-binding protein with emerging endocrine functions, as a regulator of GLP-1 biogenesis in intestinal L-cells. Using absolute qPCR and immunofluorescence, we found that HuD was significantly expressed in the GLUTag cells derived from mice intestinal L-cell line and was co-localized with GLP-1-positive cells in the small intestine of mice. RNA interference-mediated HuD knockdown reduced both GLP-1 immunoreactivity and levels. Mechanistically, RNA immunoprecipitation and biotinylated 3'UTR pull-down demonstrated that HuD binds to the mRNAs of the and (PC1/3) genes. The levels of the proglucagon (∼17 kDa) and PC1/3 proteins decreased without significant changes in their mRNAs, suggesting post-transcriptional control. Metabolic stress converged on this module: palmitate decreased proglucagon/PC1/3 in GLUTag cells, and a high-fat diet reduced GLP-1 and PC1/3 signals in the mouse intestine. Interestingly, zinc sulfate partially restored proglucagon and PC1/3 levels following palmitate treatment. These findings reveal a HuD-/ axis is crucial for GLP-1 biogenesis and which is susceptible to lipotoxic stress. - Source: PubMed
Publication date: 2025/12/15
Han SukyoungJung MyeongwooRyu SeungyeonCha SeonghoTak HyosunJeong Seung MinLee Eun Kyung - Alzheimer's disease (AD) is characterized by widespread molecular dysregulation, with the APOEe4 allele recognized as its strongest genetic risk factor. However, the mechanisms by which APOEe4 drives distinct molecular changes - whether by exacerbating pathology or triggering compensatory responses - remain incompletely understood. We generated and analyzed proteomic, epigenetic, and genetic data from post-mortem dorsolateral prefrontal cortex samples of a uniquely APOEe4-enriched subset of the Religious Orders Study and Memory and Aging Project (ROSMAP). Specifically, we generated DIA LC-MS proteomic data (n = 302), analyzed previously generated DNA methylation profiles from our group (n = 310), and used published whole-genome sequencing data (n = 254) to compute polygenic risk scores (PRS). In this cohort, 69% (n = 214) were APOEe4 carriers, and 19.6% (n = 42) of them showed no pathological evidence of AD based on NIA-Reagan criteria, enabling identification of APOEe4-related risk and resilience mechanisms. In the absence of AD, APOEe4 carriers exhibited lower levels of 27 proteins, suggesting early synaptic (e.g., VAMP1, SYN3, CASKIN1) and metabolic (e.g., GLUD1, PI4KA) vulnerability. By contrast, APOEe4 carriers with AD displayed marked upregulation of inflammatory and proteostatic proteins (e.g., GNAO1, AHNAK, FGG, HEBP1, APEX1, RAB4A, SLC12A5, LRP1, BAG6) and hypermethylation of cg06329447 in ELAVL4. Network analyses highlighted convergent disruptions in synaptic transmission, metabolism, and proteostasis - key pathways altered in APOEe4-associated AD. Mediation analyses identified GRIPAP1 and GSTK1 as top protein mediators (accounting for ~26-33% of APOEe4's effect), with VAMP1, CASKIN1, DPP3, SYN3, and FGG each contributing ~9-15%. ELAVL4 hypermethylation also mediated ~12% of the APOEe4 effect, linking epigenetic dysregulation to disease risk. To assess whether the identified proteins reflected broader genetic risk for AD or were specific to APOEe4, we calculated PRS both excluding and including the APOE genomic region. While the non-APOE PRS showed no association with identified molecular markers, the APOE-inclusive PRS was significantly associated with eight AD-related proteins in carriers, indicating they are not explained by polygenic risk outside of APOE. Finally, predictive modeling stratified by APOEe4 status revealed that in non-carriers, PRS most effectively classified AD (AUC = 0.73), whereas in carriers, proteomic and epigenetic markers outperformed PRS (AUC up to 0.74). Together, these findings demonstrate that APOEe4 confers AD risk through early synaptic and metabolic disruptions and later-stage inflammatory and epigenetic changes, laying the groundwork for genotype-tailored biomarker development and therapeutic strategies. - Source: PubMed
Publication date: 2025/10/16
Markov YaroslavPriyanka AhanaXu LeqiWang WeiweiThrush-Evensen KyraGonzalez JohnBorrus DanielKasamoto JessicaSehgal RaghavZou GraceFraij JenelCarlyle Becky CHorvath SteveBennett David AZhao Hongyuvan Dyck Christopher HLam TuKiet TLevine Morgan EHiggins-Chen Albert T