eIF5A binds to translational machinery components and affects translation in yeast

Zanelli, Cleslei Fernando; Maragno, Ana L. C.; Gregio, Ana Paula Borges; Komili, Suzanne; Pandolfi, J. R. C.; Mestriner, Carlos Alberto; Lustri, Wilton R.; Valentini, Sandro Roberto

doi:10.1016/j.bbrc.2006.07.195

Cited by 94 publications

(127 citation statements)

References 51 publications

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“…Yeast eIF5A was found to interact with the translational machinery (Jao and Chen 2006;Zanelli et al 2006;Saini et al 2009), and depletion of eIF5A impaired protein synthesis and yeast cell growth (Kang and Hershey 1994;Saini et al 2009;Henderson and Hershey 2011). Analysis of polyribosome profiles of yeast depleted of eIF5A or following inactivation of a temperature-sensitive eIF5A mutant revealed retention of polysomes in the absence of cycloheximide (CHX), indicating a defect in translation elongation (Gregio et al 2009;Saini et al 2009).…”

Section: Eif5a Promotion Of Peptide Bond Formationmentioning

confidence: 99%

Mechanism and Regulation of Protein Synthesis in Saccharomyces cerevisiae

2016

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In this review, we provide an overview of protein synthesis in the yeast Saccharomyces cerevisiae. The mechanism of protein synthesis is well conserved between yeast and other eukaryotes, and molecular genetic studies in budding yeast have provided critical insights into the fundamental process of translation as well as its regulation. The review focuses on the initiation and elongation phases of protein synthesis with descriptions of the roles of translation initiation and elongation factors that assist the ribosome in binding the messenger RNA (mRNA), selecting the start codon, and synthesizing the polypeptide. We also examine mechanisms of translational control highlighting the mRNA cap-binding proteins and the regulation of GCN4 and CPA1 mRNAs.

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Section: Eif5a Promotion Of Peptide Bond Formationmentioning

confidence: 99%

Mechanism and Regulation of Protein Synthesis in Saccharomyces cerevisiae

2016

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“…This finding implies that eIF5A Hyp is required for linking Nos2 mRNA to the translational machinery. Prior studies have shown that yeast homolog of eIF5A interacts directly with components of the translational machinery and is necessary for translational elongation (53,66).…”

Section: Figure 10mentioning

confidence: 99%

The unique hypusine modification of eIF5A promotes islet β cell inflammation and dysfunction in mice

et al. 2010

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In both type 1 and type 2 diabetes, pancreatic islet dysfunction results in part from cytokine-mediated inflammation. The ubiquitous eukaryotic translation initiation factor 5A (eIF5A), which is the only protein to contain the amino acid hypusine, contributes to the production of proinflammatory cytokines. We therefore investigated whether eIF5A participates in the inflammatory cascade leading to islet dysfunction during the development of diabetes. As described herein, we found that eIF5A regulates iNOS levels and that eIF5A depletion as well as the inhibition of hypusination protects against glucose intolerance in inflammatory mouse models of diabetes. We observed that following knockdown of eIF5A expression, mice were resistant to β cell loss and the development of hyperglycemia in the low-dose streptozotocin model of diabetes. The depletion of eIF5A led to impaired translation of iNOS-encoding mRNA within the islet. A role for the hypusine residue of eIF5A in islet inflammatory responses was suggested by the observation that inhibition of hypusine synthesis reduced translation of iNOS-encoding mRNA in rodent β cells and human islets and protected mice against the development of glucose intolerance the low-dose streptozotocin model of diabetes. Further analysis revealed that hypusine is required in part for nuclear export of iNOS-encoding mRNA, a process that involved the export protein exportin1. These observations identify the hypusine modification of eIF5A as a potential therapeutic target for preserving islet function under inflammatory conditions.

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“…Interestingly, eIF5A is the only known protein to undergo a unique and essential posttranslational modification to form the hypusine residue, and this modification is necessary for its interaction with the 80S ribosome (Jao and Chen 2006;Zanelli et al 2006). eIF5A was initially described to be involved in the formation of the first peptide bond in translation initiation (Benne and Hershey 1978).…”

mentioning

confidence: 99%

Fertility and Polarized Cell Growth Depends on eIF5A for Translation of Polyproline-Rich Formins in Saccharomyces cerevisiae

Belda-Palazón

Ferrando

et al. 2014

Genetics

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eIF5A is an essential and evolutionary conserved translation elongation factor, which has recently been proposed to be required for the translation of proteins with consecutive prolines. The binding of eIF5A to ribosomes occurs upon its activation by hypusination, a modification that requires spermidine, an essential factor for mammalian fertility that also promotes yeast mating. We show that in response to pheromone, hypusinated eIF5A is required for shmoo formation, localization of polarisome components, induction of cell fusion proteins, and actin assembly in yeast. We also show that eIF5A is required for the translation of Bni1, a prolinerich formin involved in polarized growth during shmoo formation. Our data indicate that translation of the polyproline motifs in Bni1 is eIF5A dependent and this translation dependency is lost upon deletion of the polyprolines. Moreover, an exogenous increase in Bni1 protein levels partially restores the defect in shmoo formation seen in eIF5A mutants. Overall, our results identify eIF5A as a novel and essential regulator of yeast mating through formin translation. Since eIF5A and polyproline formins are conserved across species, our results also suggest that eIF5A-dependent translation of formins could regulate polarized growth in such processes as fertility and cancer in higher eukaryotes.

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eIF5A binds to translational machinery components and affects translation in yeast

Cited by 94 publications

References 51 publications

Mechanism and Regulation of Protein Synthesis in Saccharomyces cerevisiae

Mechanism and Regulation of Protein Synthesis in Saccharomyces cerevisiae

The unique hypusine modification of eIF5A promotes islet β cell inflammation and dysfunction in mice

Fertility and Polarized Cell Growth Depends on eIF5A for Translation of Polyproline-Rich Formins in Saccharomyces cerevisiae

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