ArticlePLoS genetics2012
CELF4 regulates translation and local abundance of a vast set of mRNAs, including genes associated with regulation of synaptic function.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 4 of them syntheses that pooled it.
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Who cites it
84 citing papers in PubMed, 4 syntheses or guidelines pooled it, 131 citations in OpenAlex.
- Adaptation of the Porcine Pituitary Transcriptome, Spliceosome and Editome during Early Pregnancy.International journal of molecular sciences · 2023Pooled it
- Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions.Nature neuroscience · 2019Pooled it
- Biological annotation of genetic loci associated with intelligence in a meta-analysis of 87,740 individuals.Molecular psychiatry · 2019Pooled it
- Genome-wide analysis of over 106 000 individuals identifies 9 neuroticism-associated loci.Molecular psychiatry · 2016Pooled it
- Analytical and clinical validation of the EdenDx methylation assay as a noninvasive supportive triage tool for early detection of endometrial cancer in cervical scraping specimens.Gynecologic oncology reports · 2026Article
- Spinal Cord CELF4 in Chronic Constriction Injury-Induced Neuropathic Pain: Association with TRPV1 and COX-2 Expression.Journal of molecular neuroscience : MN · 2026Article
- CELF family of RNA-binding proteins: roles in disease biology and potential for therapeutic intervention.Cell communication and signaling : CCS · 2026Review
- Celf4 Regulates Excitability of Bushy Cells in the Cochlear Nucleus of the Mouse Brainstem.Cellular and molecular neurobiology · 2026Article
- Unraveling the core: hub genes bridging familial and sporadic Parkinson's disease.Journal of neurology · 2026Article
- The RNA-binding protein CELF4: from molecular regulatory networks to clinical translation in cross-system diseases.Frontiers in molecular biosciences · 2026Review
- Development and validation of hypermethylated gene markers in cervical cytological samples for detecting endometrial cancer (EndoMethy-I trial).Frontiers in oncology · 2026Article
- The genetic architecture of fibromyalgia across 2.5 million individuals.medRxiv : the preprint server for health sciences · 2025Article
- Genome-wide association analysis revealed novel candidate genes for body measurement traits in indigenous Gudali and crossbred Simgud in Cameroon.BMC genomics · 2025Article
- Heterozygous CELF4 variants in the N-term region crucial for the RNA-binding activity lead to neurodevelopmental disorder and obesity.European journal of human genetics : EJHG · 2025Article
- Review
- Neonatal Encephalopathy: Novel Phenotypes and Genotypes Identified by Genome Sequencing.Neurology. Genetics · 2025Article
- A genome-wide association study of occupational creativity and its relations with well-being and career success.Communications biology · 2024Article
- Identifying regulatory elements and their RNA-binding proteins in the 3' untranslated regions of papillomavirus late mRNAs.Biomedical reports · 2024Article
- Social Determinants of Health in Cardio-Oncology: Multi-Level Strategies to Overcome Disparities in Care:JACC. CardioOncology · 2024Review
- Altered CELF4 splicing factor enhances pancreatic neuroendocrine tumors aggressiveness influencing mTOR and everolimus response.Molecular therapy. Nucleic acids · 2024Article
24 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
RNA-binding proteins have emerged as causal agents of complex neurological diseases. Mice deficient for neuronal RNA-binding protein CELF4 have a complex neurological disorder with epilepsy as a prominent feature. Human CELF4 has recently been associated with clinical features similar to those seen in mutant mice. CELF4 is expressed primarily in excitatory neurons, including large pyramidal cells of the cerebral cortex and hippocampus, and it regulates excitatory but not inhibitory neurotransmission. We examined mechanisms underlying neuronal hyperexcitability in Celf4 mutants by identifying CELF4 target mRNAs and assessing their fate in the absence of CELF4 in view of their known functions. CELF4 binds to at least 15%-20% of the transcriptome, with striking specificity for the mRNA 3' untranslated region. CELF4 mRNA targets encode a variety of proteins, many of which are well established in neuron development and function. While the overall abundance of these mRNA targets is often dysregulated in Celf4 deficient mice, the actual expression changes are modest at the steady-state level. In contrast, by examining the transcriptome of polysome fractions and the mRNA distribution along the neuronal cell body-neuropil axis, we found that CELF4 is critical for maintaining mRNA stability and availability for translation. Among biological processes associated with CELF4 targets that accumulate in neuropil of mutants, regulation of synaptic plasticity and transmission are the most prominent. Together with a related study of the impact of CELF4 loss on sodium channel Na(v)1.6 function, we suggest that CELF4 deficiency leads to abnormal neuronal function by combining a specific effect on neuronal excitation with a general impairment of synaptic transmission. These results also expand our understanding of the vital roles RNA-binding proteins play in regulating and shaping the activity of neural circuits.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.