PKC Regulates YAP Expression through Alternative Splicing of YAP 3′UTR Pre-mRNA by hnRNP F
The Yes-associated protein (YAP) is a transcriptional co-activator that plays critical roles in organ development and tumorigenesis, and is verified to be inhibited by the Hippo signaling pathway. In the present study, we show that the YAP 3′UTR is alternatively spliced to generate a novel 950 bp 3′...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-01-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/2/694 |
| _version_ | 1797412578351120384 |
|---|---|
| author | Wing-Keung Chu Li-Man Hung Chun-Wei Hou Jan-Kan Chen |
| author_facet | Wing-Keung Chu Li-Man Hung Chun-Wei Hou Jan-Kan Chen |
| author_sort | Wing-Keung Chu |
| collection | DOAJ |
| description | The Yes-associated protein (YAP) is a transcriptional co-activator that plays critical roles in organ development and tumorigenesis, and is verified to be inhibited by the Hippo signaling pathway. In the present study, we show that the YAP 3′UTR is alternatively spliced to generate a novel 950 bp 3′UTR mRNA from the full length 3′UTR region (3483 bp) in human cancer cells. The ratio of full length 3′UTR YAP mRNA to alternatively spliced 3′UTR YAP mRNA is up-regulated by exposure of the cells to PKC inhibitor chelerythrine chloride. Further study using luciferase reporter assay showed that the expression of the alternatively spliced 3′UTR mRNA is much lower compared with the full length 3′UTR mRNA, suggesting that alternatively spliced 3′UTR YAP mRNA may have a shorter half-life than full length 3′UTR mRNA. Interestingly, PKC represses YAP 3′UTR–mediated mRNA stability is dependent on a splicing factor, hnRNP F. Activation of PKC induces nuclear translocation of cytosolic hnRNP F. Ectopic expression of hnRNP F enhances YAP 3′UTR splicing. Our results suggest that hnRNP F regulates YAP 3′UTR-mediated mRNA stability in an alternative splicing-dependent manner, and PKC regulated YAP expression is dependent on nuclear translocation of hnRNP F in human cancer cell lines. |
| first_indexed | 2024-03-09T05:05:11Z |
| format | Article |
| id | doaj.art-86e4a2b05be346ca88a0760ed4ae7514 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T05:05:11Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-86e4a2b05be346ca88a0760ed4ae75142023-12-03T12:55:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-0122269410.3390/ijms22020694PKC Regulates YAP Expression through Alternative Splicing of YAP 3′UTR Pre-mRNA by hnRNP FWing-Keung Chu0Li-Man Hung1Chun-Wei Hou2Jan-Kan Chen3Healthy Aging Research Center, Chang Gung University, Taoyuan 33302, TaiwanHealthy Aging Research Center, Chang Gung University, Taoyuan 33302, TaiwanHealthy Aging Research Center, Chang Gung University, Taoyuan 33302, TaiwanHealthy Aging Research Center, Chang Gung University, Taoyuan 33302, TaiwanThe Yes-associated protein (YAP) is a transcriptional co-activator that plays critical roles in organ development and tumorigenesis, and is verified to be inhibited by the Hippo signaling pathway. In the present study, we show that the YAP 3′UTR is alternatively spliced to generate a novel 950 bp 3′UTR mRNA from the full length 3′UTR region (3483 bp) in human cancer cells. The ratio of full length 3′UTR YAP mRNA to alternatively spliced 3′UTR YAP mRNA is up-regulated by exposure of the cells to PKC inhibitor chelerythrine chloride. Further study using luciferase reporter assay showed that the expression of the alternatively spliced 3′UTR mRNA is much lower compared with the full length 3′UTR mRNA, suggesting that alternatively spliced 3′UTR YAP mRNA may have a shorter half-life than full length 3′UTR mRNA. Interestingly, PKC represses YAP 3′UTR–mediated mRNA stability is dependent on a splicing factor, hnRNP F. Activation of PKC induces nuclear translocation of cytosolic hnRNP F. Ectopic expression of hnRNP F enhances YAP 3′UTR splicing. Our results suggest that hnRNP F regulates YAP 3′UTR-mediated mRNA stability in an alternative splicing-dependent manner, and PKC regulated YAP expression is dependent on nuclear translocation of hnRNP F in human cancer cell lines.https://www.mdpi.com/1422-0067/22/2/694alternative splicinghnRNP FPKC3′UTR |
| spellingShingle | Wing-Keung Chu Li-Man Hung Chun-Wei Hou Jan-Kan Chen PKC Regulates YAP Expression through Alternative Splicing of YAP 3′UTR Pre-mRNA by hnRNP F International Journal of Molecular Sciences alternative splicing hnRNP F PKC 3′UTR |
| title | PKC Regulates YAP Expression through Alternative Splicing of YAP 3′UTR Pre-mRNA by hnRNP F |
| title_full | PKC Regulates YAP Expression through Alternative Splicing of YAP 3′UTR Pre-mRNA by hnRNP F |
| title_fullStr | PKC Regulates YAP Expression through Alternative Splicing of YAP 3′UTR Pre-mRNA by hnRNP F |
| title_full_unstemmed | PKC Regulates YAP Expression through Alternative Splicing of YAP 3′UTR Pre-mRNA by hnRNP F |
| title_short | PKC Regulates YAP Expression through Alternative Splicing of YAP 3′UTR Pre-mRNA by hnRNP F |
| title_sort | pkc regulates yap expression through alternative splicing of yap 3 utr pre mrna by hnrnp f |
| topic | alternative splicing hnRNP F PKC 3′UTR |
| url | https://www.mdpi.com/1422-0067/22/2/694 |
| work_keys_str_mv | AT wingkeungchu pkcregulatesyapexpressionthroughalternativesplicingofyap3utrpremrnabyhnrnpf AT limanhung pkcregulatesyapexpressionthroughalternativesplicingofyap3utrpremrnabyhnrnpf AT chunweihou pkcregulatesyapexpressionthroughalternativesplicingofyap3utrpremrnabyhnrnpf AT jankanchen pkcregulatesyapexpressionthroughalternativesplicingofyap3utrpremrnabyhnrnpf |