"We have tested three individual Rbfox3 proteins in alternative splicing assays and find that all of these Rbfox3 protein isoforms repress inclusion of the alternative RRM exon, exon 6, of Rbfox2, giving rise to a variant of Rbfox2 without a functional RRM"

"alternative splicing of the Rbfox3 pre-mRNA itself leads to the production of four protein isoforms that migrate in the 45-50 kDa range"

"Rbfox3-regulated alternative splicing of Numb promotes neuronal differentiation during development"

"Mice lacking RBFOX3 show deficits in adult hippocampal neurogenesis, evidenced by reduced proliferation or survival of newborn neurons in the dentate gyrus"

"RBFOX3 knockout leads to altered expression of synapse-related gene isoforms, an increase in dendritic spine density (indicative of aberrant synapse formation)"

"A study of Rolandic epilepsy found a de novo nonsense mutation in RBFOX3 (p.Tyr287*) and an exon 3 deletion, among other RBFOX-family mutations, in patients"

"Rbfox3 homozygous knockout mice displayed deficits in neurogenesis, which was correlated with cognitive impairments"

"Synaptic plasticity and density, which are related to cognitive behaviors, were altered in the hippocampal dentate gyrus of Rbfox3 homozygous knockout mice; synaptic plasticity decreased and the density of synapses increased"

"Furthermore, RBFOX3 regulates the exons of genes with synapse-related function"

"Dysfunction of RBFOX3 has been identified in neurodevelopmental disorders such as autism spectrum disorder, cognitive impairments and epilepsy and a causal relationship with these diseases has been previously demonstrated"

"RBFOX3 (312 aa) is the shortest family member, significantly smaller than RBFOX1 (397 aa) and RBFOX2 (390 aa). Shows only 6-8% sequence identity to RBFOX1/2 in overlapping regions, indicating significant functional specialization despite conserved RRM domain"

"RRM domain (aa 100-175, 76 residues) contains canonical RNP1 motif (RQMFGQF) at position 116 and experimentally validated RNA interaction sites. High content of aromatic and basic residues supports RNA binding function"

"Domain structure and binding site analysis confirm recognition of UGCAUG canonical motif with position-dependent splicing regulation mechanism. Known targets include RBFOX2, NUMB, GRIA2, and CACNA1C"

"High proline content (12.8%) in disordered regions, unique domain architecture, and target gene analysis provide structural basis for neuronal tissue specificity and alternative splicing regulation"

"A 2018 study confirmed that RBFOX3 (NeuN) binds Tau pre-mRNA and enhances exon 10 splicing, with deletion of RBFOX3's RRM or its binding sites abolishing this effect"

"A study of Rolandic epilepsy found a de novo nonsense mutation in RBFOX3 (p.Tyr287*) and an exon 3 deletion, among other RBFOX-family mutations, in patients"

"Three highly correlated single-nucleotide polymorphisms in RBFOX3 showed genome-wide significance for longer sleep latency (P ~10^-8), and follow-up analysis across ~30,000 individuals confirmed this association"

"In HIV-associated neurocognitive disorder, RBFOX3 (NeuN) mislocalization from the nucleus to the cytoplasm has been observed in affected neurons, which could disrupt normal splicing of neuron-specific transcripts"

"RBFOX proteins are known to function as part of a large spliceosomal assembly (the Large Assembly of Splicing Regulators) via their C-termini, interacting with other splicing co-factors to exert their effects on exon inclusion"

"RBFOX3 was upregulated in HCC tumors and cell lines, and knocking it down inhibited cancer cell proliferation. RBFOX3 knockdown also made the HCC cells more sensitive to the chemotherapy drug 5-fluorouracil"

"RBFOX3 is a member of the RBFOX family of splicing regulators that share a single central **RNA-recognition motif (RRM)** and preferentially bind the cis-element **(U)GCAUG**, using a **position-dependent** mechanism to activate or repress alternative exons."

"binding downstream of an alternative exon tends to enhance exon inclusion, whereas binding upstream tends to repress inclusion"

"RBFOX3 binds a **conserved upstream intronic UGCAUG element** near an alternative exon and represses its inclusion. In vivo and in-development loss-of-function experiments support that RBFOX3-dependent Numb splicing promotes neuronal differentiation."

"nuclear RBFOX3 isoforms promote inclusion of cryptic RBFOX2 exons that introduce premature termination codons and target RBFOX2 transcripts for nonsense-mediated decay (NMD)."

"Beyond pre-mRNA splicing, RBFOX3 binds pri-miRNAs and modulates their processing by the Drosha microprocessor. PAR-CLIP identified RBFOX3 binding clusters on pri-miRNAs"

"RBFOX3v2 is mainly nuclear and RBFOX3v3 is mainly cytoplasmic; the cytoplasmic isoform may still access the nucleus (potential shuttling), allowing it to regulate splicing."

"RBFOX3 is largely neuron-restricted, whereas RBFOX1 is expressed in neurons as well as muscle/heart and RBFOX2 has broader expression across tissues/cell types."

"summarizes the position-dependent mechanism and network-level operation of RBFOX proteins (including LASR association and noncanonical recruitment)"

"Rbfox3 enhanced tau exon 10 inclusion. Tau intron 10 contains UGCAUG, the conservative binding sequence of Rbfox3. Intron 10 of tau pre-mRNA was co-immunoprecipitated by Rbfox3/NeuN. Deletion mutants of the RNA recognition motif (RRM) or three RNA-binding sites of the RRM in Rbfox3/NeuN failed to enhance tau exon 10 inclusion."

"we found significantly higher NeuN reactivity in the cytoplasm of neurons in brain sections from HIV-infected individuals with cognitive impairment compared to controls"

"We found a cluster of three highly correlated variants (rs9900428, rs9907432 and rs7211029) in the RNA-binding protein fox-1 homolog 3 gene (RBFOX3) associated with sleep latency"

"this gene is significantly involved in the release cycle of neurotransmitters including gamma-aminobutyric acid and various monoamines"

"Exome sequencing of 242 RE patients revealed two novel probably deleterious variants in RBFOX1, a frameshift mutation (p.A233Vfs*74) and a hexanucleotide deletion (p.A299_A300del), and a novel nonsense mutation in RBFOX3 (p.Y287*)"

"nuclear Rbfox proteins are bound within a large assembly of splicing regulators (LASR), a multimeric complex containing the proteins hnRNP M, hnRNP H, hnRNP C, Matrin3, NF110/NFAR-2, NF45, and DDX5"

"NeuN was recently eventually identified as an epitope of Rbfox3, which is a novel member of the Rbfox1 family of splicing factors"

"this role has been challenged by recent studies indicating that NeuN staining is variable and even absent during certain diseases and specific physiological states"