University of Oulu

Jan Vrbský, Vladimir Vinarský, Ana Rubina Perestrelo, Jorge Oliver De La Cruz, Fabiana Martino, Antonio Pompeiano, Valerio Izzi, Ota Hlinomaz, Vladimir Rotrekl, Marius Sudol, Stefania Pagliari, Giancarlo Forte, Evidence for discrete modes of YAP1 signaling via mRNA splice isoforms in development and diseases, Genomics, Volume 113, Issue 3, 2021, Pages 1349-1365, ISSN 0888-7543, https://doi.org/10.1016/j.ygeno.2021.03.009

Evidence for discrete modes of YAP1 signaling via mRNA splice isoforms in development and diseases

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Author: Vrbský, Jan1; Vinarský, Vladimir1,2; Perestrelo, Ana Rubina1;
Organizations: 1International Clinical Research Center (ICRC), St Anne's University Hospital, CZ-65691 Brno, Czech Republic
2Competence Center for Mechanobiology in Regenerative Medicine, INTERREG ATCZ133, CZ-62500 Brno, Czech Republic
3Department of Biology, Masaryk University, CZ-62500 Brno, Czech Republic
4University of Oulu, FI-90014 Oulu, Finland
5Finnish Cancer Institute, 00130 Helsinki, Finland
6Department of Physiology, Yong Loo Li School of Medicine, Block MD9, 2 Medical Drive #04-01, 117597, Singapore
7Mechanobiology Institute, T-Lab, 5A Engineering Drive 1, 117411, Singapore
8Department of Medicine, Icahn School of Medicine at Mount Sinai, NY, New York 10029, United States of America
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 9.7 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2021051029391
Language: English
Published: Elsevier, 2021
Publish Date: 2021-05-10
Description:

Abstract

Yes-associated protein 1 (YAP1) is a transcriptional co-activator downstream of Hippo pathway. The pathway exerts crucial roles in organogenesis and its dysregulation is associated with the spreading of different cancer types. YAP1 gene encodes for multiple protein isoforms, whose specific functions are not well defined. We demonstrate the splicing of isoform-specific mRNAs is controlled in a stage- and tissue-specific fashion. We designed expression vectors encoding for the most-represented isoforms of YAP1 with either one or two WW domains and studied their specific signaling activities in YAP1 knock-out cell lines. YAP1 isoforms display both common and unique functions and activate distinct transcriptional programs, as the result of their unique protein interactomes. By generating TEAD-based transcriptional reporter cell lines, we demonstrate individual YAP1 isoforms display unique effects on cell proliferation and differentiation. Finally, we illustrate the complexity of the regulation of Hippo-YAP1 effector in physiological and in pathological conditions of the heart.

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Series: Genomics
ISSN: 0888-7543
ISSN-E: 1089-8646
ISSN-L: 0888-7543
Volume: 113
Issue: 3
Pages: 1349 - 1365
DOI: 10.1016/j.ygeno.2021.03.009
OADOI: https://oadoi.org/10.1016/j.ygeno.2021.03.009
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
3122 Cancers
Subjects:
Funding: This work was supported by the European Regional Development Fund - Project MAGNET (No. CZ.02.1.01/0.0/0.0/15_003/0000492) and the European Regional Development Fund in frame of the project Kompetenzzentrum MechanoBiologie (ATCZ133) in the Interreg V-A Austria - Czech Republic programme. M.S. would like to acknowledge generous grants from the National University of Singapore (R-185-000-2710-133 and -733), the Mechanobiology Institute (MBI) (R-714-018-006-271), and the Institute of Molecular and Cell Biology (M-R02010).
Copyright information: © 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
  https://creativecommons.org/licenses/by-nc-nd/4.0/