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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′...

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Autores principales: Chu, Wing-Keung, Hung, Li-Man, Hou, Chun-Wei, Chen, Jan-Kan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828143/
https://www.ncbi.nlm.nih.gov/pubmed/33445676
http://dx.doi.org/10.3390/ijms22020694
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author Chu, Wing-Keung
Hung, Li-Man
Hou, Chun-Wei
Chen, Jan-Kan
author_facet Chu, Wing-Keung
Hung, Li-Man
Hou, Chun-Wei
Chen, Jan-Kan
author_sort Chu, Wing-Keung
collection PubMed
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.
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spelling pubmed-78281432021-01-25 PKC Regulates YAP Expression through Alternative Splicing of YAP 3′UTR Pre-mRNA by hnRNP F Chu, Wing-Keung Hung, Li-Man Hou, Chun-Wei Chen, Jan-Kan Int J Mol Sci Article 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. MDPI 2021-01-12 /pmc/articles/PMC7828143/ /pubmed/33445676 http://dx.doi.org/10.3390/ijms22020694 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chu, Wing-Keung
Hung, Li-Man
Hou, Chun-Wei
Chen, Jan-Kan
PKC Regulates YAP Expression through Alternative Splicing of YAP 3′UTR Pre-mRNA by hnRNP F
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828143/
https://www.ncbi.nlm.nih.gov/pubmed/33445676
http://dx.doi.org/10.3390/ijms22020694
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