RBFOX2-regulated TEAD1 alternative splicing plays a pivotal role in Hippo-YAP signaling. Issue 15 (14th June 2022)

• Record Type: Journal Article
• Authors: Choi, Sunkyung; Lee, Hyo Seong; Cho, Namjoon; Kim, Inyoung; Cheon, Seongmin; Park, Chungoo; Kim, Eun-Mi; Kim, Wantae; Kim, Kee K
• Is Part Of: Nucleic acids research. Volume 50:Issue 15(2022)
• Page Start: 8658
• Page End: 8673
• Publication Date: 2022-06-14
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkac509
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: Alternative pre-mRNA splicing is key to proteome diversity; however, the biological roles of alternative splicing (AS) in signaling pathways remain elusive. Here, we focus on TEA domain transcription factor 1 (TEAD1), a YAP binding factor in the Hippo signaling pathway. Public database analyses showed that expression of YAP-TEAD target genes negatively correlated with the expression of a TEAD1 isoform lacking exon 6 (TEAD1 ΔE6 ) but did not correlate with overall TEAD1 expression. We confirmed that the transcriptional activity and oncogenic properties of the full-length TEAD1 isoform were greater than those of TEAD1 ΔE6, with the difference in transcription related to YAP interaction. Furthermore, we showed that RNA-binding Fox-1 homolog 2 (RBFOX2) promoted the inclusion of TEAD1 exon 6 via binding to the conserved GCAUG element in the downstream intron. These results suggest a regulatory mechanism of RBFOX2-mediated TEAD1 AS and provide insight into AS-specific modulation of signaling pathways. Graphical Abstract: