Biology Commons^™

Hits-Clip And Integrative Modeling Define The Rbfox Splicing-Regulatory Network Linked To Brain Development And Autism, Natalie Farny, Sebastien Weyn-Vanhentenryck, Aldo Mele, Qinghong Yan, Shuying Sun, Zuo Zhang, Chenghai Xue, Margaret Herre, Pamela Silver, Michael Zhang, Adrian Krainer, Robert Darnell, Chaolin Zhang

Natalie G. Farny

The RNA binding proteins Rbfox1/2/3 regulate alternative splicing in the nervous system, and disruption of Rbfox1 has been implicated in autism. However, comprehensive identification of functional Rbfox targets has been challenging. Here, we perform HITS-CLIP for all three Rbfox family members in order to globally map, at a single-nucleotide resolution, their in vivo RNA interaction sites in the mouse brain. We find that the two guanines in the Rbfox binding motif UGCAUG are critical for protein-RNA interactions and crosslinking. Using integrative modeling, these interaction sites, combined with additional datasets, define 1,059 direct Rbfox target alternative splicing events. Over half of …