The Drosophila gene Rbfox1, as a putative target of the microRNA Dmel\mir-980, was assessed using an intermediate-term olfactory-aversive memory assay. (The role of mir-980 is described in the human disease model report 'neurodevelopmental disorders, susceptibility to (postulated), MIR22-related, FBhh0001101.) Mutations of Dmel\Rbfox1, which has three predicted mir-980-binding sites in its 3' UTR, exhibit significant memory impairment in this assay. RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated for Rbfox1.
There are three human genes orthologous to Dmel\Rbfox1, RBFOX1, RBFOX2 and RBFOX3. They are members of the Fox-1 family of RNA-binding proteins, which are known to regulate tissue-specific alternative splicing. RBFOX1 has been tentatively associated with neurodevelopmental dysfunction in a number of contexts and diseases, including susceptibility to autism and intellectual disability. The human Hsap\RBFOX1 gene has been introduced into flies, but has not been characterized.
Dmel\Rbfox1 is an LCD (low complexity sequence domain)-containing protein. It has been demonstrated that, like other LCD-containing RNA-binding proteins, the Rbfox1 protein aggregates into liquid droplets and amyloid-like fibers and joins different nuclear and cytoplasmic RNP granules. Characterized as a component of response to stress (using protein starvation or elevated temperature), it was found that reduced expression of Dmel\mir-980 during stress leads to increased Rbfox1 levels, widespread formation of various RNP granules, and increased cell viability.
Ubiquitous knockdown of Dmel\Rbfox1, effected by RNAi, typically results in lethality during the larval stage. With less profound loss, animals survive to adulthood; females are sterile. Adults with RNAi-mediated knockdown targeted to all neural tissues or to the mushroom bodies of the brain exhibit memory impairment. Overexpression of Rbfox1 in the mushroom bodies enhances memory. Multiple genetic and physical interactions have been described for Dmel\Rbfox1; see below and in the Rbfox1 gene report.
[updated Feb. 2020 by FlyBase; FBrf0222196]
Various studies have postulated that RBFOX1 is associated with epilepsy, susceptibility to autism, and intellectual disability (FBrf0231056 and references cited therein).
Diseases associated with RBFOX1 include Benign Epilepsy With Centrotemporal Spikes and Developmental Coordination Disorder. [Gene Cards, RBFOX1; 2019.07.24]
The Fox-1 family of RNA-binding proteins is evolutionarily conserved, and regulates tissue-specific alternative splicing in metazoa. [Gene Cards, RBFOX1; 2019.07.24]
Many to one: 3 human to 1 Drosophila.
Moderate-scoring ortholog of human RBFOX1, RBFOX2, RBFOX3 (1 Drosophila to 3 human). Dmel\Rbfox1 shares 32-34% identity and 41-42% similarity with RBFOX1 and RBFOX2; it less closely related to RBFOX3.
