RBFOX3

RBFOX3, also known as FOX-3 or NeuN, is a vertebrate RNA-binding protein encoded by the RBFOX3 gene. It is the third member of the RBFOX family (RBFOX1-3) characterized by a conserved RNA recognition motif (RRM). The RBFOX proteins are widely studied for their roles in RNA processing in neurons.

RBFOX3 binds RNA sequences containing UGCAUG and related motifs and participates in the regulation of alternative splicing of many neuronally expressed transcripts. Through its splicing activity, RBFOX3 contributes to neuronal differentiation, maturation, and synaptic function, often by promoting neuron-specific splice isoforms and suppressing others. It can act cooperatively with other splicing factors and may influence mRNA stability and localization in neurons.

Expression of RBFOX3 is enriched in neurons of the central and peripheral nervous system. The protein is predominantly localized to the nucleus, consistent with a role in splicing, though cytoplasmic localization has been observed in some contexts. The NeuN antibody, widely used in neuroscience, recognizes RBFOX3 and is employed as a marker of mature neurons in immunohistochemistry and histology.

RBFOX3 is part of a conserved RBFOX gene family that also includes RBFOX1 and RBFOX2, each with overlapping but distinct tissue patterns and splicing targets. Alterations in RBFOX3 expression or function have been associated with neurological disorders in some studies, and animal models show that RBFOX3-dependent splicing programs are important for normal neuronal development and function. Ongoing research seeks to clarify its precise targets and mechanisms in human health and disease.