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


VRBSKY Jan VINARSKY Vladimir PERESTRELO Ana Rubina DE LA CRUZ Jorge Oliver MARTINO Fabiana POMPEIANO Antonio IZZI Valerio HLINOMAZ Ota ROTREKL Vladimír SUDOL Marius PAGLIARI Stefania FORTE Giancarlo

Rok publikování 2021
Druh Článek v odborném periodiku
Časopis / Zdroj Genomics
Fakulta / Pracoviště MU

Lékařská fakulta

www https://www.sciencedirect.com/science/article/pii/S0888754321001014?via%3Dihub
Doi http://dx.doi.org/10.1016/j.ygeno.2021.03.009
Klíčová slova YAP1 isoforms; Alternative splicing; Tissue-specific expression; Cardiac differentiation
Popis 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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