Translation of yes-associated protein (YAP) was antagonized by its circular RNA via suppressing the assembly of the translation initiation machinery

Yap is the key component of Hippo pathway which plays crucial roles in tumorigenesis. Inhibition of Yap activity could promote apoptosis, suppress proliferation, and restrain metastasis of cancer cells. However, how Yap is regulated is not fully understood. Here, we reported Yap being negatively reg...

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Autores principales: Wu, Nan, Yuan, Zhidong, Du, Kevin Y., Fang, Ling, Lyu, Juanjuan, Zhang, Chao, He, Alina, Eshaghi, Esra, Zeng, Kaixuan, Ma, Jian, Du, William W., Yang, Burton B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224378/
https://www.ncbi.nlm.nih.gov/pubmed/31092884
http://dx.doi.org/10.1038/s41418-019-0337-2
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author Wu, Nan
Yuan, Zhidong
Du, Kevin Y.
Fang, Ling
Lyu, Juanjuan
Zhang, Chao
He, Alina
Eshaghi, Esra
Zeng, Kaixuan
Ma, Jian
Du, William W.
Yang, Burton B.
author_facet Wu, Nan
Yuan, Zhidong
Du, Kevin Y.
Fang, Ling
Lyu, Juanjuan
Zhang, Chao
He, Alina
Eshaghi, Esra
Zeng, Kaixuan
Ma, Jian
Du, William W.
Yang, Burton B.
author_sort Wu, Nan
collection PubMed
description Yap is the key component of Hippo pathway which plays crucial roles in tumorigenesis. Inhibition of Yap activity could promote apoptosis, suppress proliferation, and restrain metastasis of cancer cells. However, how Yap is regulated is not fully understood. Here, we reported Yap being negatively regulated by its circular RNA (circYap) through the suppression of the assembly of Yap translation initiation machinery. Overexpression of circYap in cancer cells significantly decreased Yap protein but did not affect its mRNA levels. As a consequence, it remarkably suppressed proliferation, migration and colony formation of the cells. We found that circYap could bind with Yap mRNA and the translation initiation associated proteins, eIF4G and PABP. The complex containing overexpressed circYap abolished the interaction of PABP on the poly(A) tail with eIF4G on the 5′-cap of the Yap mRNA, which functionally led to the suppression of Yap translation initiation. Individually blocking the binding sites of circYap on Yap mRNA or respectively mutating the binding sites for PABP and eIF4G derepressed Yap translation. Significantly, breast cancer tissue from patients in the study manifested dysregulation of circYap expression. Collectively, our study uncovered a novel molecular mechanism in the regulation of Yap and implicated a new function of circular RNA, supporting the pursuit of circYap as a potential tool for future cancer intervention.
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spelling pubmed-72243782020-05-15 Translation of yes-associated protein (YAP) was antagonized by its circular RNA via suppressing the assembly of the translation initiation machinery Wu, Nan Yuan, Zhidong Du, Kevin Y. Fang, Ling Lyu, Juanjuan Zhang, Chao He, Alina Eshaghi, Esra Zeng, Kaixuan Ma, Jian Du, William W. Yang, Burton B. Cell Death Differ Article Yap is the key component of Hippo pathway which plays crucial roles in tumorigenesis. Inhibition of Yap activity could promote apoptosis, suppress proliferation, and restrain metastasis of cancer cells. However, how Yap is regulated is not fully understood. Here, we reported Yap being negatively regulated by its circular RNA (circYap) through the suppression of the assembly of Yap translation initiation machinery. Overexpression of circYap in cancer cells significantly decreased Yap protein but did not affect its mRNA levels. As a consequence, it remarkably suppressed proliferation, migration and colony formation of the cells. We found that circYap could bind with Yap mRNA and the translation initiation associated proteins, eIF4G and PABP. The complex containing overexpressed circYap abolished the interaction of PABP on the poly(A) tail with eIF4G on the 5′-cap of the Yap mRNA, which functionally led to the suppression of Yap translation initiation. Individually blocking the binding sites of circYap on Yap mRNA or respectively mutating the binding sites for PABP and eIF4G derepressed Yap translation. Significantly, breast cancer tissue from patients in the study manifested dysregulation of circYap expression. Collectively, our study uncovered a novel molecular mechanism in the regulation of Yap and implicated a new function of circular RNA, supporting the pursuit of circYap as a potential tool for future cancer intervention. Nature Publishing Group UK 2019-05-15 2019-12 /pmc/articles/PMC7224378/ /pubmed/31092884 http://dx.doi.org/10.1038/s41418-019-0337-2 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Wu, Nan
Yuan, Zhidong
Du, Kevin Y.
Fang, Ling
Lyu, Juanjuan
Zhang, Chao
He, Alina
Eshaghi, Esra
Zeng, Kaixuan
Ma, Jian
Du, William W.
Yang, Burton B.
Translation of yes-associated protein (YAP) was antagonized by its circular RNA via suppressing the assembly of the translation initiation machinery
title Translation of yes-associated protein (YAP) was antagonized by its circular RNA via suppressing the assembly of the translation initiation machinery
title_full Translation of yes-associated protein (YAP) was antagonized by its circular RNA via suppressing the assembly of the translation initiation machinery
title_fullStr Translation of yes-associated protein (YAP) was antagonized by its circular RNA via suppressing the assembly of the translation initiation machinery
title_full_unstemmed Translation of yes-associated protein (YAP) was antagonized by its circular RNA via suppressing the assembly of the translation initiation machinery
title_short Translation of yes-associated protein (YAP) was antagonized by its circular RNA via suppressing the assembly of the translation initiation machinery
title_sort translation of yes-associated protein (yap) was antagonized by its circular rna via suppressing the assembly of the translation initiation machinery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224378/
https://www.ncbi.nlm.nih.gov/pubmed/31092884
http://dx.doi.org/10.1038/s41418-019-0337-2
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