Yeast Translation Elongation Factor eIF5A Expression Is Regulated by Nutrient Availability through Different Signalling Pathways

• Published in: International journal of molecular sciences 2020-12, Vol.22 (1), p.219
• Main Authors: Barba-Aliaga, Marina, Villarroel-Vicente, Carlos, Stanciu, Alice, Corman, Alba, Martínez-Pastor, María Teresa, Alepuz, Paula
• Format: Article
• Language: English
• Subjects: Aerobiosis - drug effects; Amino acids; Carbon - pharmacology; Carbon sources; Citric Acid Cycle - drug effects; Depletion; Down-Regulation - drug effects; Down-Regulation - genetics; eIF5A; Elongation; Enzymes; Eukaryotes; Eukaryotic Translation Initiation Factor 5A; Fermentation; Fermentation - drug effects; Gene expression; Gene Expression Regulation, Fungal - drug effects; Glucose; Glucose - metabolism; Hap1; Heme; Heme - metabolism; Iron - metabolism; Iron Deficiencies; Isoforms; Kinases; Lysine - analogs & derivatives; Lysine - metabolism; Mammals; Mechanistic Target of Rapamycin Complex 1 - metabolism; Metabolic Flux Analysis; Metabolism; Metastases; Mitochondria; mitochondrial respiration; Models, Biological; Nutrient availability; Nutrients; Oxygen consumption; Peptide Initiation Factors - metabolism; Phosphorylation; Polyamines; Protein Isoforms - metabolism; Proteins; Respiration; Ribosomes; RNA-Binding Proteins - metabolism; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - growth & development; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism; Signal transduction; Signal Transduction - drug effects; TOR; Transcription factors; Translation; Translation elongation; Up-Regulation - drug effects; Up-Regulation - genetics; Yeast
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22010219

Translation elongation factor eIF5A binds to ribosomes to promote peptide bonds between problematic amino acids for the reaction like prolines. eIF5A is highly conserved and essential in eukaryotes, which usually contain two similar but differentially expressed paralogue genes. The human eIF5A-1 isoform is abundant and implicated in some cancer types; the eIF5A-2 isoform is absent in most cells but becomes overexpressed in many metastatic cancers. Several reports have connected eIF5A and mitochondria because it co-purifies with the organelle or its inhibition reduces respiration and mitochondrial enzyme levels. However, the mechanisms of eIF5A mitochondrial function, and whether eIF5A expression is regulated by the mitochondrial metabolism, are unknown. We analysed the expression of yeast eIF5A isoforms Tif51A and Tif51B under several metabolic conditions and in mutants. The depletion of Tif51A, but not Tif51B, compromised yeast growth under respiration and reduced oxygen consumption. Tif51A expression followed dual positive regulation: by high glucose through TORC1 signalling, like other translation factors, to promote growth and by low glucose or non-fermentative carbon sources through Snf1 and heme-dependent transcription factor Hap1 to promote respiration. Upon iron depletion, Tif51A was down-regulated and Tif51B up-regulated. Both were Hap1-dependent. Our results demonstrate eIF5A expression regulation by cellular metabolic status.