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EIF5A1 Isoform A Can Modulate the Metabolism in HeLa Cells
Author(s) -
Pereira Karina Danielle,
Tamborlin Leticia,
Meneguello Leticia,
Bomfim Lucas Henrique Montes,
Proença Andre Ricardo Gomes,
Melo Carlos Fernando Odir Rodrigues,
Catharino Rodrigo Ramos,
Reis Silveira Leonardo,
Luchessi Augusto Ducati
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb208
Subject(s) - gene isoform , biology , amino acid , microbiology and biotechnology , biochemistry , gene
The eukaryotic translation initiation factor 5A (eIF5A) is widespread in Archaea and Eukarya and contains the unusual amino acid residue hypusine. Recent studies have shown its involvement in the elongation step of translation. More specifically, acting on the synthesis of proteins containing polyproline stretches. The eIF5A has been involved in different physiological and pathological processes, such as inflammation, cancer, diabetes and virus infection. In humans, different transcript variants related to eIF5A1 are currently registered in databases. Recently, we observed that the transcript variant A is characterized by an additional upstream start codon in‐frame with the canonical initiation codon. Therefore, the product of this transcript, eIF5A1 isoform A, has a N‐terminal extension of 30 amino acid residues, when compared to the canonical isoform B. In addition it was evidenced that the isoform A connects to mitochondria. Thus, the objective of the present study is to evaluate the functionality of eIF5A1 isoform A. HeLa cells were transfected with siRNA‐VA1/2 or siRNA Control and analyzed after 72 and 96 hours. As result, it was observed that the depletion of transcript variant A correlates with reduction in cellular viability and cell cycle arrest. The metabolic profile analysis of these cells revealed that the alternative eIF5A1 isoform has some role in metabolic homeostasis. Indeed, causing negative effects on energy metabolism, as revealed by reduction in lactate production and in the content of transcripts related to mitochondria activity and biogenesis. Thus, it is proposed that eIF5A isoform A protein may modulates the cellular metabolism by acting on oxidative process controlled by mitochondria. Support or Funding Information São Paulo Research Foundation (FAPESP)