RBFOX2-regulated TEAD1 alternative splicing plays a pivotal role in Hippo-YAP signaling

Sunkyung Choi, Hyo Seong Lee, Namjoon Cho, Inyoung Kim, Seongmin Cheon, Chungoo Park, Eun Mi Kim, Wantae Kim, Kee K. Kim

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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 (TEAD1ΔE6) 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 TEAD1ΔE6, 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.

Original languageEnglish
Pages (from-to)8658-8673
Number of pages16
JournalNucleic Acids Research
Volume50
Issue number15
DOIs
StatePublished - 26 Aug 2022

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