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- W2558246499 abstract "[eng] The Cytoplasmic Polyadenylation Element Binding (CPEB)-family of RNA-binding proteins is composed of four paralogs in mammals, CPEB1-4. The CPEBs control the translation of the targeted mRNAs by modulating the length of their poly(A) tail. This regulatory mechanism activates maternally stored mRNAs in oocytes and drives oocyte maturation and early embryogenesis. Genome-wide studies have revealed that the CPEBs are expressed in various adult tissues and potentially regulate up to 20% of the vertebrate transcriptome. However, the specific roles and regulation of each CPEB are poorly understood beyond the embryonic stage. In this study, we aimed to define the functions and regulation of CPEB4 in adult tissues of mammalian organisms. For this purpose, we have generated ubiquitous and tissue-specific loss of function mouse models for CPEB4. The characterization of these genetic models has revealed that CPEB4-mediated translation is essential for mammalian organisms to cope with metabolic stress. Moreover, we have identified the molecular mechanism by which CPEB4 establishes a translational program to maintain cellular homeostasis during metabolically challenging conditions. Altogether, our results reveal a novel function of CPEB4 in gene expression regulation during metabolic stress. [spa] La familia de proteinas CPEB (Cytoplasmic Polyadenylation Element Binding Protein) engloba cuatro paralogos en mamiferos: CPEB1-4. Las CPEBs controlan la traduccion de los RNAs mensajeros (mRNAs) mediante la regulacion de la longitud de la cola de poli(A) de los mismos. Este mecanismo se encarga de activar la traduccion de los mRNAs maternos en ovocitos y por ello dirige la el ciclo meiotico y el desarrollo embrionario temprano. Estudios genomicos y proteomicos de amplio espectro han revelado que las CPEBs se expresan en varios tejidos adultos y regulan colectivamente el 20% del genoma de los vertebrados. Sin embargo, se desconoce la funcion y regulacion de las distintas CPEBs mas alla del desarollo embrionario. El objetivo de este estudio ha sido definir las funciones y regulacion de CPEB4 en tejidos adultos de mamiferos. Para ello, hemos generado modelos geneticos de perdida de funcion de CPEB4 en ratones, tanto ubicuos como especificos de tejido. La caracterizacion de estos modelos geneticos ha desvelado que la regulacion mediada por CPEB4 es esencial para la adaptacion del organismo a diversos estreses metabolicos. Ademas, hemos identificado los mecanismos moleculares mediante los cuales CPEB4 genera un circuito de traduccion celular que mantiene la homeostasis celular durante condiciones metabolicas adversas. En conjunto, nuestro estudio revela una nueva funcion de CPEB4 en la regulacion de la expresion genica durante estres metabolico." @default.
- W2558246499 created "2016-12-08" @default.
- W2558246499 creator A5002836811 @default.
- W2558246499 date "2016-06-21" @default.
- W2558246499 modified "2023-09-23" @default.
- W2558246499 title "Essential functions of Cpeb4 in tissue homeostasis" @default.
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- W2558246499 hasPublicationYear "2016" @default.
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