Heterogeneous ribonucleoprotein F regulates YAP expression via a G-tract in 3'UTR

Wing-Keung Chu; Li-Man Hung; Chun-Wei Hou; Jan-Kan Chen

doi:10.1016/j.bbagrm.2018.10.003

Heterogeneous ribonucleoprotein F regulates YAP expression via a G-tract in 3'UTR

Biochim Biophys Acta Gene Regul Mech. 2019 Jan;1862(1):12-24. doi: 10.1016/j.bbagrm.2018.10.003. Epub 2018 Oct 10.

Authors

Wing-Keung Chu¹, Li-Man Hung², Chun-Wei Hou³, Jan-Kan Chen⁴

Affiliations

¹ Department of Physiology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; Healthy and Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan.
² Healthy and Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan; Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
³ Healthy and Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan.
⁴ Department of Physiology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; Healthy and Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan. Electronic address: jkc508@mail.cgu.edu.tw.

PMID: 30312683
DOI: 10.1016/j.bbagrm.2018.10.003

Abstract

The Yes-associated protein (YAP) is a transcription coactivator that plays crucial roles in organ size control and tumorigenesis, and was demonstrated to be inhibited by the Hippo signaling pathway. To date, the molecular mechanisms regulating the expression of YAP in human cells remain unknown. In the present study, we found that hnRNP F and hnRNP U negatively regulate YAP expression. We also showed that downregulation of YAP expression by hnRNP F and hnRNP U was not at the transcriptional level. Knockdown of hnRNP F or hnRNP U increased YAP mRNA stability, suggesting the downregulation of YAP expression was by a post-transcriptional mechanism. A putative hnRNP F binding site was identified in the YAP 3'UTR at 685 to 698, and deletion of this putative hnRNP F element abolished the down-regulation effect of YAP mRNA stability by hnRNP F. Binding of the hnRNP F to the YAP 3'UTR was demonstrated by Cross-linked RNA Immunoprecipitation. mRNA stability is a possible secondary effect of alternative splicing or other nuclear process. Understanding the regulation of YAP expression would provide insights into the mechanisms underlying the maintenance of tissue size homeostasis and tumorigenesis.

Keywords: 3′UTR; Tumorigenesis; YAP; hnRNP F; mRNA stability.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3' Untranslated Regions / genetics*
Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism*
Binding Sites
Cell Line, Tumor
Down-Regulation
Gene Expression Regulation*
Heterogeneous-Nuclear Ribonucleoprotein Group F-H / physiology*
Heterogeneous-Nuclear Ribonucleoprotein U / physiology
Humans
PC-3 Cells
Phosphoproteins / genetics
Phosphoproteins / metabolism*
RNA Processing, Post-Transcriptional
RNA Stability
Transcription Factors
YAP-Signaling Proteins

Substances

3' Untranslated Regions
Adaptor Proteins, Signal Transducing
Heterogeneous-Nuclear Ribonucleoprotein Group F-H
Heterogeneous-Nuclear Ribonucleoprotein U
Phosphoproteins
Transcription Factors
YAP-Signaling Proteins
YAP1 protein, human