Hypusinated eIF5A s required for the translation of collagen
Por:
Barba-Aliaga M, Mena A, Espinoza V, Apostolova N, Costell M and Alepuz P
Publicada:
1 sep 2021
Ahead of Print:
27 sep 2021
Categoría:
Cell biology
Resumen:
Translation of mRNAs that encode peptide sequences with consecutive prolines (polyproline) requires the conserved and essential elongation factor eIF5A to facilitate the formation of peptide bonds. It has been shown that, upon eIF5A depletion, yeast ribosomes stall in polyproline motifs, but also in tripeptide sequences that combine proline with glycine and charged amino acids. Mammalian collagens are enriched in putative eIF5A-dependent Pro-Gly-containing tripeptides. Here, we show that depletion of active eIF5A in mouse fibroblasts reduced collagen type I alpha 1 chain (Col1a1) content, which concentrated around the nuclei. Moreover, it provoked the upregulation of endoplasmic reticulum (ER) stress markers, suggesting retention of partially synthesized collagen 1 (Col1) in the ER. We confirmed that eIF5A is needed for heterologous collagen synthesis in yeast and, using a double luciferase reporter system, showed that eIF5A depletion interrupts translation at Pro-Gly collagenic motifs. A dramatically lower level of Col1a1 protein was also observed in functional eIF5A-depleted human hepatic stellate cells treated with the profibrotic cytokine TGF-beta 1. In sum, our results show that collagen expression requires eIF5A and imply its potential as a target for regulating collagen production in fibrotic diseases.
Filiaciones:
Barba-Aliaga M:
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universitat de València, C/ Dr. Moliner 50, E46100 Burjassot, Spain
Instituto Biotecmed, Universitat de València, C/Dr. Moliner 50, E46100 Burjassot, Spain
Mena A:
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universitat de València, C/ Dr. Moliner 50, E46100 Burjassot, Spain
Instituto Biotecmed, Universitat de València, C/Dr. Moliner 50, E46100 Burjassot, Spain
Espinoza V:
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universitat de València, C/ Dr. Moliner 50, E46100 Burjassot, Spain
Instituto Biotecmed, Universitat de València, C/Dr. Moliner 50, E46100 Burjassot, Spain
:
Departamento de Farmacología, Facultad de Medicina, Universitat de València, E46010 Valencia, Spain
Centro de Investigación Biomédica en Red: enfermedades hepáticas y digestivas (CIBERehd), Spain
FISABIO, Hospital Universitario Dr. Peset, Valencia, Spain
Costell M:
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universitat de València, C/ Dr. Moliner 50, E46100 Burjassot, Spain
Instituto Biotecmed, Universitat de València, C/Dr. Moliner 50, E46100 Burjassot, Spain
Alepuz P:
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universitat de València, C/ Dr. Moliner 50, E46100 Burjassot, Spain
Instituto Biotecmed, Universitat de València, C/Dr. Moliner 50, E46100 Burjassot, Spain
Bronze, Green Submitted
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