Essential functions of Cpeb4 in tissue homeostasis
[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...
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| Format: | doctoral thesis |
| Status: | Published version |
| Publication Date: | 2016 |
| Country: | España |
| Institution: | Universidad de Barcelona |
| Repository: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/104251 |
| Online Access: | https://hdl.handle.net/2445/104251 http://hdl.handle.net/10803/398127 |
| Access Level: | Open access |
| Keyword: | Citoplasma Proteïnes Genètica Cytoplasm Proteins Genetics |
| Summary: | [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. |
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