دورية أكاديمية
Hypusinated eIF5A is required for the translation of collagen.
| العنوان: | Hypusinated eIF5A is required for the translation of collagen. |
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| المؤلفون: | 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., Apostolova N; 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. |
| المصدر: | Journal of cell science [J Cell Sci] 2021 Sep 15; Vol. 134 (18). Date of Electronic Publication: 2021 Sep 27. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Company of Biologists Country of Publication: England NLM ID: 0052457 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1477-9137 (Electronic) Linking ISSN: 00219533 NLM ISO Abbreviation: J Cell Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Cambridge : Company of Biologists Original Publication: London. |
| مواضيع طبية MeSH: | Peptide Initiation Factors*/genetics , Peptide Initiation Factors*/metabolism , RNA-Binding Proteins*/genetics, Animals ; Collagen/genetics ; Mice ; Ribosomes/metabolism ; Saccharomyces cerevisiae/metabolism |
| مستخلص: | 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 α1 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-β1. In sum, our results show that collagen expression requires eIF5A and imply its potential as a target for regulating collagen production in fibrotic diseases. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2021. Published by The Company of Biologists Ltd.) |
| فهرسة مساهمة: | Keywords: Collagen; ER stress; Fibrosis; Translation; eIF5A |
| المشرفين على المادة: | 0 (Peptide Initiation Factors) 0 (RNA-Binding Proteins) 9007-34-5 (Collagen) |
| تواريخ الأحداث: | Date Created: 20210827 Date Completed: 20211026 Latest Revision: 20211026 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1242/jcs.258643 |
| PMID: | 34447991 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1477-9137 |
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| DOI: | 10.1242/jcs.258643 |