@article{e035a21d851449f4a6f44459430f4081,
title = "Identification of dynamic RNA-binding proteins uncovers a Cpeb4-controlled regulatory cascade during pathological cell growth of cardiomyocytes",
abstract = "RNA-binding proteins (RBPs) control critical aspects of cardiomyocyte function, but the repertoire of active RBPs in cardiomyocytes during the growth response is largely unknown. We define RBPs in healthy and diseased cardiomyocytes at a system-wide level by RNA interactome capture. This identifies 67 cardiomyocyte-specific RBPs, including several contractile proteins. Furthermore, we identify the cytoplasmic polyadenylation element-binding protein 4 (Cpeb4) as a dynamic RBP, regulating cardiac growth both in vitro and in vivo. We identify mRNAs bound to and regulated by Cpeb4 in cardiomyocytes. Cpeb4 regulates cardiac remodeling by differential expression of transcription factors. Among Cpeb4 target mRNAs, two zinc finger transcription factors (Zeb1 and Zbtb20) are discovered. We show that Cpeb4 regulates the expression of these mRNAs and that Cpeb4 depletion increases their expression. Thus, Cpeb4 emerges as a critical regulator of cardiomyocyte function by differential binding to specific mRNAs in response to pathological growth stimulation.",
keywords = "Cpeb4, RBPs, Zeb1, cardiomycoytes, pathological hypertrophy",
author = "Eva Riechert and Vivien Kmietczyk and Frank Stein and Thomas Schwarzl and Thileepan Sekaran and Lonny J{\"u}rgensen and Verena Kamuf-Schenk and Eshita Varma and Christoph Hofmann and Mandy Rettel and Kira G{\"u}r and Julie {\"O}lschl{\"a}ger and Friederike K{\"u}hl and Judit Martin and Marta Ramirez-Pedraza and Mercedes Fernandez and Shirin Doroudgar and Ra{\'u}l M{\'e}ndez and Katus, {Hugo A.} and Hentze, {Matthias W.} and Mirko V{\"o}lkers",
note = "Funding Information: We thank all members of the M.V. laboratory for helpful discussion and comments. We thank Jordan Graphics for illustration of graphical schemes. H.A.K. and M.V. acknowledge the DZHK (German Centre for Cardiovascular Research) Partner Site Heidelberg/Mannheim. This work was supported by grants from the Spanish Ministry of Science, Innovation and Universities (BFU2017-83561-P to R.M.; SAF2017-87988-R to M.F.) and by the Scientific Foundation, Spanish Association Against Cancer, the Worldwide Cancer Research Foundation, the BBVA Foundation, ?la Caixa? Foundation, and the Fundaci? la Marat? de TV3 to R.M. and M.F. IRB Barcelona is the recipient of a Severo Ochoa Award of Excellence from MINECO (Government of Spain) and is supported by the CERCA Programme (Catalan Government). M.V. is supported by the Deutsche Forschungsgemeinschaft, the Plus 3 Programme of the Boehringer Ingelheim Foundation (BISI), and by Baden-W?rttemberg Stiftung. We thank Marcos Fernandez for reviewing the manuscript. Conceptualization: M.V.; methodology: E.R. M.W.H. and M.V.; investigation: E.R. V.K. L.J, V.K.-S. E.V. M.R. S.D. K.G, J.?. F.K. J.M. M.R.-P. and M.F.; data curation: F.S. T. Schwarzl, T. Sekaran, and C.H.; formal analysis: T. Schwarzl, F.S. T. Sekaran, and C.H.; writing ? original draft, M.V. and E.R.; writing ? review & editing: all authors; funding acquisition: H.A.K. and M.V.; resources: S.D. H.A.K. R.M. M.W.H. and M.V; supervision: M.V. and M.W.H. The authors declare no competing interests. We worked to ensure diversity in experimental samples through the selection of the cell lines. Funding Information: We thank all members of the M.V. laboratory for helpful discussion and comments. We thank Jordan Graphics for illustration of graphical schemes. H.A.K. and M.V. acknowledge the DZHK (German Centre for Cardiovascular Research) Partner Site Heidelberg/Mannheim. This work was supported by grants from the Spanish Ministry of Science, Innovation and Universities ( BFU2017-83561-P to R.M.; SAF2017-87988-R to M.F.) and by the Scientific Foundation, Spanish Association Against Cancer , the Worldwide Cancer Research Foundation , the BBVA Foundation , “la Caixa” Foundation , and the Fundaci{\'o} la Marat{\'o} de TV3 to R.M. and M.F. IRB Barcelona is the recipient of a Severo Ochoa Award of Excellence from MINECO ( Government of Spain ) and is supported by the CERCA Programme ( Catalan Government ). M.V. is supported by the Deutsche Forschungsgemeinschaft , the Plus 3 Programme of the Boehringer Ingelheim Foundation (BISI), and by Baden-W{\"u}rttemberg Stiftung . We thank Marcos Fernandez for reviewing the manuscript. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = may,
day = "11",
doi = "10.1016/j.celrep.2021.109100",
language = "English (US)",
volume = "35",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "6",
}