A Translational Regulatory Mechanism Mediated by Hypusinated Eukaryotic Initiation Factor 5A Facilitates β-Cell Identity and Function.

Autor:	Connors CT; Department of Biology, Indiana University Indianapolis, Indianapolis, IN., Villaca CBP; Department of Biology, Indiana University Indianapolis, Indianapolis, IN., Anderson-Baucum EK; Indiana Biosciences Research Institute, Indianapolis, IN., Rosario SR; Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY., Rutan CD; Department of Biology, Indiana University Indianapolis, Indianapolis, IN., Childress PJ; Indiana Biosciences Research Institute, Indianapolis, IN., Padgett LR; Indiana Biosciences Research Institute, Indianapolis, IN., Robertson MA; Department of Biology, Indiana University Indianapolis, Indianapolis, IN., Mastracci TL; Department of Biology, Indiana University Indianapolis, Indianapolis, IN.; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN.; Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN.
Jazyk:	angličtina
Zdroj:	Diabetes [Diabetes] 2024 Mar 01; Vol. 73 (3), pp. 461-473.
DOI:	10.2337/db23-0148
Abstrakt:	As professional secretory cells, β-cells require adaptable mRNA translation to facilitate a rapid synthesis of proteins, including insulin, in response to changing metabolic cues. Specialized mRNA translation programs are essential drivers of cellular development and differentiation. However, in the pancreatic β-cell, the majority of factors identified to promote growth and development function primarily at the level of transcription. Therefore, despite its importance, the regulatory role of mRNA translation in the formation and maintenance of functional β-cells is not well defined. In this study, we have identified a translational regulatory mechanism mediated by the specialized mRNA translation factor eukaryotic initiation factor 5A (eIF5A), which facilitates the maintenance of β-cell identity and function. The mRNA translation function of eIF5A is only active when it is posttranslationally modified ("hypusinated") by the enzyme deoxyhypusine synthase (DHPS). We have discovered that the absence of β-cell DHPS in mice reduces the synthesis of proteins critical to β-cell identity and function at the stage of β-cell maturation, leading to a rapid and reproducible onset of diabetes. Therefore, our work has revealed a gatekeeper of specialized mRNA translation that permits the β-cell, a metabolically responsive secretory cell, to maintain the integrity of protein synthesis necessary during times of induced or increased demand. (© 2024 by the American Diabetes Association.)
Databáze:	MEDLINE
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