PUBLICATION
Hypusinated and unhypusinated isoforms of the translation factor eIF5A exert distinct effects in models of pancreas development and function
- Authors
- Anderson, C.M., Kulkarni, A., Maier, B., Huang, F., Figatner, K., Chakraborty, A., Pratuangtham, S., May, S.C., Tersey, S.A., Anderson, R.M., Mirmira, R.G.
- ID
- ZDB-PUB-250121-24
- Date
- 2025
- Source
- The Journal of biological chemistry : 108209108209 (Journal)
- Registered Authors
- Keywords
- eIF5A, hypusine, mouse, pancreas, polyamines, translation, zebrafish
- Datasets
- GEO:GSE279773
- MeSH Terms
-
- RNA-Binding Proteins*/genetics
- RNA-Binding Proteins*/metabolism
- Eukaryotic Translation Initiation Factor 5A*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Oxidoreductases Acting on CH-NH Group Donors/genetics
- Oxidoreductases Acting on CH-NH Group Donors/metabolism
- Mice
- Lysine/analogs & derivatives
- Animals
- Insulin-Secreting Cells/metabolism
- Protein Isoforms/genetics
- Protein Isoforms/metabolism
- Pancreas*/growth & development
- Pancreas*/metabolism
- Zebrafish*/genetics
- Zebrafish*/growth & development
- Zebrafish*/metabolism
- Peptide Initiation Factors*/genetics
- Peptide Initiation Factors*/metabolism
- PubMed
- 39832654 Full text @ J. Biol. Chem.
Citation
Anderson, C.M., Kulkarni, A., Maier, B., Huang, F., Figatner, K., Chakraborty, A., Pratuangtham, S., May, S.C., Tersey, S.A., Anderson, R.M., Mirmira, R.G. (2025) Hypusinated and unhypusinated isoforms of the translation factor eIF5A exert distinct effects in models of pancreas development and function. The Journal of biological chemistry. :108209108209.
Abstract
Hypusination of eukaryotic translation initiation factor 5A (eIF5A) is essential for its role in translation elongation and termination. Although the function of hypusinated eIF5A (eIF5AHyp) in cellular proliferation is well-characterized, the role of its unhypusinated form (eIF5ALys) remains unclear. We hypothesized that eIF5ALys exerts independent, negative effects on cellular replication and metabolism, distinct from the loss of eIF5AHyp. To test this hypothesis, we utilized zebrafish and mouse models with inducible knockdowns of deoxyhypusine synthase (DHPS) and eIF5A to investigate their roles in cellular growth. Gene expression analysis via RNA sequencing and morphometric measurements of pancreas and β-cell mass were performed to assess phenotypic changes and identify affected biological pathways. Loss of DHPS in zebrafish resulted in significant defects in pancreatic growth, accompanied by changes in gene expression related to mRNA translation, neurogenesis, and stress pathways. By contrast, knockdown of eIF5A had minimal impact on pancreas development, suggesting that the effects of DHPS loss are not solely due to the lack of eIF5AHyp. In mice, β cell-specific deletion of DHPS impaired β cell mass expansion and glucose tolerance, while eIF5A deletion had no statistically significant effects. These findings provide evidence for an independent role for eIF5ALys in regulating developmental and functional responses in pancreas health and disease.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping