Gene Ontology annotation through association of InterPro records with GO terms.
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara.
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods.
RNA-binding analyses of HuC and HuD with the VEGF and c-myc 3'-untranslated regions using a novel ELISA-based assay.
Protein interaction studies in human induced neurons indicate convergent biology underlying autism spectrum disorders.
Using brain cell-type-specific protein interactomes to interpret neurodevelopmental genetic signals in schizophrenia.
The molecular genetics of nELAVL in brain development and disease.
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ELAVL3 is the only nELAVL expressed in Purkinje neurons; Elavl3 knockout mice develop progressive cerebellar ataxia with disrupted Purkinje synaptic formation, swollen axons, and neuronal transport deficits, and Elavl3+/- and -/- mice show seizure activity.
"As Elavl3−/− mice aged, progressive severe cerebellar ataxia was observed. This ataxia caused an abnormal step cycle, tremor and over time, impaired postural reflexes. At the cellular level, Purkinje neurons had disrupted synaptic formation, swollen axons, and overall deficits in neuronal transport, highlighting the requirement for Elavl3 activity in these neurons"
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ELAVL3 regulates alternative splicing of neuronal transcripts converging on glutamate regulation and excitability, including embryonic-specific inclusion of AnkG exon 34; ELAVL3 also drives 3'-UTR lengthening via distal poly(A) site usage during inhibitory neuron differentiation.
"High-throughput sequencing analysis of alternative splicing in the cerebellum of Elavl3−/− mice highlighted the convergence of targeted transcripts on glutamate levels and neuronal excitability—linking RNA regulation to the seizure activity observed in Elavl3−/− mice"
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All four ELAVL proteins share three RNA recognition motifs (RRMs) with a hinge region; RRM1 and RRM2 directly bind AU-rich elements in 3'-UTRs, while RRM3 supports transcript stability via poly(A)-associated mechanisms.
"Binding to RNA targets is facilitated by the RRM1 and RRM2 domains preferentially recognising AU-rich elements in the 3ʹUTR of transcripts"
Long 3'UTRs predispose neurons to inflammation by promoting immunostimulatory double-stranded RNA formation.
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The neuron-enriched ELAVL family (ELAVL2, ELAVL3, ELAVL4) collectively drives 3'-UTR lengthening in human neurons, which in turn raises dsRNA load and tonically activates dsRNA-sensing PRRs (MDA5, PKR, TLR3).
"the neuron-enriched ELAVL family of genes (ELAVL2, ELAVL3, and ELAVL4) can increase (i) 3'UTR length, (ii) dsRNA load, and (iii) activation of dsRNA-sensing PRRs such as MDA5, PKR, and TLR3"
High-resolution epitope mapping of anti-Hu and anti-Yo autoimmunity by programmable phage display.
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ELAVL3/HuC is one of the neuronal ELAVL (nELAVL) proteins targeted by anti-Hu paraneoplastic autoantibodies; the dominant immunodominant epitope maps to a 17-residue motif in the hinge region between RRM2 and RRM3 shared across ELAVL2/3/4, with most enriched peptides (>80%) attributed to ELAVL4.
"A majority (>90%) of the significantly enriched nELAVL peptides converged upon on a 17-residue sequence at AA positions 276–294 of ELAVL4, a sequence which is also common to variants of ELAVL2 and ELAVL3"
ELAV/Hu RNA-binding protein family - key regulators in neurological disorders, cancer, and other diseases.
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ELAVL3 is restricted to the nervous system, essential for cerebellar function, and involved in neuronal differentiation and excitability; ELAVL3 dysregulation is associated with epilepsy.
"Both Elavl3 and Elavl4 are restricted to the nervous system and are involved in neuronal differentiation and excitability. Elavl3 is essential for cerebellar function and has been associated with epilepsy"
Falcon (Edison Scientific Literature) deep research report: ELAVL3 (HuC) functional annotation
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ELAVL3 functions as a post-transcriptional regulator that uses three RRMs plus a hinge region to bind AU-/U-rich elements in 3'-UTRs, with RRM3 contributing poly(A)-tail binding; functions span splicing, APA/3'-UTR length, mRNA stability, and translation. ELAVL3 is predominantly cytoplasmic with nucleocytoplasmic shuttling.
"ELAVL3 functions primarily as a post-transcriptional regulator that stabilizes target transcripts, in part by binding AU-rich elements and influencing poly(A)-tail-associated protection; ELAVL proteins can multimerize on RNA and oppose destabilizing factors."
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ELAVL3 has a documented role in alternative splicing in which all three RRMs plus the hinge region contribute to HuC-dependent splice regulation; ELAVL3 loss alters neuronal splicing programs linked to excitability.
"ELAVL3 has a documented role in alternative splicing; all three RRMs plus the hinge region contribute to HuC-dependent splice regulation, and ELAVL3 loss alters neuronal splicing programs linked to excitability."
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ELAVL3 participates in alternative polyadenylation control of neuronal 3'-UTR length; ELAVL3 depletion shifts poly(A) usage toward proximal sites.
"ELAVL3 participates in regulation of alternative polyadenylation and 3′UTR length in neurons. ELAVL3 depletion shifts usage toward proximal poly(A) sites, whereas neuronal ELAVL proteins promote longer neuronal 3′UTRs."