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

dc.contributor.authorConnors, Craig T.
dc.contributor.authorVillaca, Catharina B. P.
dc.contributor.authorAnderson-Baucum, Emily K.
dc.contributor.authorRosario, Spencer R.
dc.contributor.authorRutan, Caleb D.
dc.contributor.authorChildress, Paul J.
dc.contributor.authorPadgett, Leah R.
dc.contributor.authorRobertson, Morgan A.
dc.contributor.authorMastracci, Teresa L.
dc.contributor.departmentBiology, School of Science
dc.date.accessioned2024-09-05T10:37:13Z
dc.date.available2024-09-05T10:37:13Z
dc.date.issued2024
dc.description.abstractAs 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.
dc.eprint.versionFinal published version
dc.identifier.citationConnors CT, Villaca CBP, Anderson-Baucum EK, et al. A Translational Regulatory Mechanism Mediated by Hypusinated Eukaryotic Initiation Factor 5A Facilitates β-Cell Identity and Function. Diabetes. 2024;73(3):461-473. doi:10.2337/db23-0148
dc.identifier.urihttps://hdl.handle.net/1805/43148
dc.language.isoen_US
dc.publisherAmerican Diabetes Association
dc.relation.isversionof10.2337/db23-0148
dc.relation.journalDiabetes
dc.rightsAttribution 4.0 United States
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourcePMC
dc.subjectEukaryotic initiation factors
dc.subjectPeptide initiation factors
dc.subjectProtein biosynthesis
dc.titleA Translational Regulatory Mechanism Mediated by Hypusinated Eukaryotic Initiation Factor 5A Facilitates β-Cell Identity and Function
dc.typeArticle
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