General Information
- Experiment ID
- OEX000084
- Experiment Name
- ZFWang_lab_NODEX00000037
- Experiment Type
- Transcriptomic
- Description
- Splicing dysregulations extensively occur in cancers, yet the biological consequences of such alterations are mostly undefined. Here we report that the Hippo-YAP signaling, a key pathway that regulates cell proliferation and organ size, is under control of a new splicing switch. We show that TEAD4, the transcription factor that mediates Hippo-YAP signaling, undergoes alternative splicing facilitated by the tumor suppressor RBM4, producing a truncated isoform, TEAD4-S, which lacks N-terminal DNA-binding domain but maintains YAP-interaction domain. TEAD4-S is located in both nucleus and cytoplasm, acting as a dominant negative isoform to YAP activity. Consistently, TEAD4-S is reduced in cancer cells, and its re-expression suppresses cancer cell proliferation and migration, inhibiting tumor growth in xenograft mouse model. Furthermore, TEAD4-S is reduced in human cancers, and patients with elevated TEAD4-S levels have improved survival. Altogether these data reveal a novel RBM4-mediated splicing switch that serves to fine-tune Hippo-YAP pathway.
- Protocol
- Cell lines stably expressing YAP, YAP/TEAD4-S, YAP/TEAD4-FL, YAP/RBM4 and control vector were created, and the total RNA was purified from the cells using TRIzol reagents. The polyadenylated RNAs were purified for construction of sequencing library using kapa TruSeq Total RNA Sample Prep kits (UNC High Throughput Sequencing Facility).
- Used ID
- NODEX00000037  
Experiment information
- Attributes
-
library_strategy RNA-seq library_layout n/a library_construction n/a library_selection n/a mate_pair n/a platform Illumina HiSeq 2000 library_name n/a - Project
-
1
Project ID Project name Create Date OEP000074 A splicing switch of TEAD4 regulates Hippo-YAP signaling pathway to inhibit tumor proliferation 2016-05-03 - Samples
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1
Sample ID Sample Name Organism Tissue Create Date OES001992 YAP-RBM4 Homo sapiens Lung Carcinom Cells 2016-05-03 - Runs
-
1
Run ID Run Name Sample Data Num Create Date OER008963 ZFWang_lab_NODER00000356 YAP-RBM4 5 2016-05-03
Author Information
- Create Date
- 2016-05-03
- Last Modified
- 2019-05-30
- Submission
- Xiaojuan Fan
- PICB