CELF2 regulation in multiple myeloma
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1279000 | ENA |
REPOSITORIES: ENA
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Project description:In this study, we analyzed transcriptome sequencing data to compare CELF2 RNA binding protein regulation in multiple myeloma cell line
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Project description:Neurodevelopment relies on precise post-transcriptional regulation to coordinate neuronal differentiation, migration, and circuit formation. The CUGBP Elav-like family member 2 (CELF2) is an RNA-binding protein with established roles in alternative splicing and mRNA regulation, yet its function in the developing brain remains poorly defined. Here, we investigated the role of CELF2 during early postnatal neurodevelopment using a constitutive Celf2 knockout mouse model. Celf2 knockout pups exhibited neonatal lethality accompanied by impaired neuronal maturation and disrupted cortical organization. Bulk RNA sequencing revealed widespread transcriptional dysregulation, while splicing analyses identified reduced exon inclusion in multiple neurodevelopmental transcripts following CELF2 loss. Notably, Camk2a transcript and protein levels were markedly reduced in knockout brains, consistent with CELF2 binding to the Camk2a 3′UTR. Functional studies in Caenorhabditis elegans demonstrated that expression of human CAMK2A partially rescued synaptic puncta deficits in unc-75 (CELF ortholog) mutants, supporting a conserved role for CELF-family proteins in synaptic maturation. Histological analyses revealed reductions in Nestin- and Doublecortin-positive immature neurons, thinning of upper cortical layers, and decreased CAMK2A expression. Single-nucleus RNA sequencing further revealed selective reductions in upper layer II/III excitatory neuron populations in the cortex. Together, these findings establish CELF2 as a critical post-transcriptional regulator required for neuronal maturation and architectural stability during early brain development and highlight how disruption of RNA regulatory programs may contribute to neurodevelopmental disorders.
2026-06-03 | GSE319281 | GEO
Project description:Neurodevelopment relies on precise post-transcriptional regulation to coordinate neuronal differentiation, migration, and circuit formation. The CUGBP Elav-like family member 2 (CELF2) is an RNA-binding protein with established roles in alternative splicing and mRNA regulation, yet its function in the developing brain remains poorly defined. Here, we investigated the role of CELF2 during early postnatal neurodevelopment using a constitutive Celf2 knockout mouse model. Celf2 knockout pups exhibited neonatal lethality accompanied by impaired neuronal maturation and disrupted cortical organization. Bulk RNA sequencing revealed widespread transcriptional dysregulation, while splicing analyses identified reduced exon inclusion in multiple neurodevelopmental transcripts following CELF2 loss. Notably, Camk2a transcript and protein levels were markedly reduced in knockout brains, consistent with CELF2 binding to the Camk2a 3′UTR. Functional studies in Caenorhabditis elegans demonstrated that expression of human CAMK2A partially rescued synaptic puncta deficits in unc-75 (CELF ortholog) mutants, supporting a conserved role for CELF-family proteins in synaptic maturation. Histological analyses revealed reductions in Nestin- and Doublecortin-positive immature neurons, thinning of upper cortical layers, and decreased CAMK2A expression. Single-nucleus RNA sequencing further revealed selective reductions in upper layer II/III excitatory neuron populations in the cortex. Together, these findings establish CELF2 as a critical post-transcriptional regulator required for neuronal maturation and architectural stability during early brain development and highlight how disruption of RNA regulatory programs may contribute to neurodevelopmental disorders.
2026-06-03 | GSE319432 | GEO
Project description:Alternative splicing is a fundamental process that contributes to the functional diversity and complexity of proteins. The regulation of each alternative splicing event involves the coordinated action of multiple RNA-binding proteins, creating a diverse array of alternatively spliced products. Dysregulation of alternative splicing is associated with various diseases, including neurodegeneration. Here we demonstrate that CELF2 binds mRNAs associated with neurodegenerative diseases, with a specific interaction observed in the intron adjacent to exon 10 on tau mRNA. Loss of CELF2 in the mouse brain results in a decreased inclusion of tau exon 10, leading to a reduced 4R:3R ratio. The hinge domain of CELF2 possesses an intrinsically disordered region (IDR), which mediates CELF2 condensation. The IDR is required for CELF2 activity in promoting tau exon 10 inclusion and can be functionally replaced by the IDRs of FUS or TAF15. With CRISPR-based imaging, we showed that CELF2 condensates colocalize with tau RNA. Using TurboID, we identified proteins that interact with CELF2 through its IDR. CELF2 co-condensates with NOVA2 and SFPQ, which coordinate with CELF2 to regulate the alternative splicing of Tau exon 10. We found that a conserved negatively charged residue within the IDR (D388) was critical for CELF2 condensate formation, its interactions with NOVA2 and SFPQ, and its function in regulating tau exon 10 splicing. Finally, we revealed that CELF2 condensation capacity is associated with 4R tau expression in vivo, impacting locomotor and cognitive function. Our data suggest that CELF2 regulates tau alternative splicing by forming condensates through its IDR with other splicing factors, and that the composition of the proteins within the condensates determines the balance of tau isoforms to impact neuronal function.
2026-07-28 | PXD070265 | Pride
Project description:<h4><strong>BACKGROUND:</strong> Multiple myeloma is characterized by clonal proliferation of malignant plasma cells in the bone marrow that produce monoclonal immunoglobulins. N-glycosylation changes of these monoclonal immunoglobulins have been reported in multiple myeloma, but previous studies only detected limited serum N-glycan features.</h4><h4><strong>METHODS:</strong> Here, a more detailed study of the human serum N-glycome of 91 multiple myeloma patients and 51 controls was performed. We additionally analyzed sequential samples from patients (n = 7) which were obtained at different time points during disease development as well as 16 paired blood serum and bone marrow plasma samples. N-glycans were enzymatically released and measured by mass spectrometry after linkage specific derivatization of sialic acids.</h4><h4><strong>RESULTS:</strong> A decrease in both α2,3- and α2,6-sialylation, galactosylation and an increase in fucosylation within complex-type N-glycans were found in multiple myeloma patients compared to controls, as well as a decrease in difucosylation of diantennary glycans. The observed glycosylation changes were present in all ISS stages, including the 'low-risk' ISS I. In individual patients, difucosylation of diantennary glycans decreased with development of the disease. Protein N-glycosylation features from blood and bone marrow showed strong correlation. Moreover, associations of monoclonal immunoglobulin (M-protein) and albumin levels with glycan traits were discovered in multiple myeloma patients.</h4><h4><strong>CONCLUSIONS & GENERAL SIGNIFICANCE: </strong>In conclusion, serum protein N-glycosylation analysis could successfully distinguish multiple myeloma from healthy controls. Further studies are needed to assess the potential roles of glycan trait changes and the associations of glycans with clinical parameters in multiple myeloma early detection and prognosis.</h4>
2022-04-27 | MTBLS676 | MetaboLights