Modeling alteration of RBFOX1 (A2BP1) target network in autism

The search for genetic risk factors for autism has revealed rare mutations in many genes. A critical step toward understanding autism is finding a common theme among the genes implicated in the disorder.

Chaolin Zhang and his colleagues at Columbia University focus on how genes are connected with each other to form molecular networks under the control of specific factors in the mammalian nervous system. One gene that the team focuses on is tissue-specific RNA-binding protein RBFOX1, which has been implicated in autism and is known to regulate splicing of neuronal transcripts.

Zhang's group developed a computational method to integrate multiple types of data, such as where RBFOX1 binds and which genes respond to its perturbation. Using this approach, they identified about 1,000 alternative splicing events that are directly regulated by RBFOX proteins1. Among these splicing events are alternative exons in 48 genes that are currently implicated in autism (e.g., TSC2). The target network suggests the potential significance of disruption in post-transcriptional regulation underlying this disorder.