Alternative Start Codon Connects eIF5A to Mitochondria

Author(s)

Pereira, Karina Danielle ; Tamborlin, Leticia ; Meneguello, Leticia ; Gomes De Proenca, Andre Ricardo ; De Paula Andrade Almeida, Isadora Cristina ; Lourenco, Rogerio Ferreira ; Luchessi, Augusto Ducati

• Document type: Journal article
• Source: Journal of Cellular Physiology; v. 231, n. 12, p. 2682-2689, DEC 2016.
• Web of Science Citations: 1

Abstract

Eukaryotic translation initiation factor 5A (eIF5A), a protein containing the amino acid residue hypusine required for its activity, is involved in a number of physiological and pathological cellular processes. In humans, several EIF5A1 transcript variants encode the canonical eIF5A1 isoform B, whereas the hitherto uncharacterized variant A is expected to code for a hypothetical eIF5A1 isoform, referred to as isoform A, which has an additional N-terminal extension. Herein, we validate the existence of eIF5A1 isoform A and its production from transcript variant A. In fact, variant A was shown to encode both eIF5A1 isoforms A and B. Mutagenic assays revealed different efficiencies in the start codons present in variant A, contributing to the production of isoform B at higher levels than isoform A. Immunoblotting and mass spectrometric analyses showed that isoform A can undergo hypusination and acetylation at specific lysine residues, as observed for isoform B. Examination of the N-terminal extension suggested that it might confer mitochondrial targeting. Correspondingly, we found that isoform A, but not isoform B, co-purified with mitochondria when the proteins were overproduced. These findings suggest that eIF5A1 isoform A has a role in mitochondrial function. (C) 2016 Wiley Periodicals, Inc. (AU)

• FAPESP's process: 14/01386-2 - The role of eukaryotic translation initiation factor 5A (EIF5A) in the translation of s6ks proteins
• Grantee: Letícia Meneguello
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 13/25263-4 - Identification and characterization of a homologue of human EIF5A isoform A in mouse
• Grantee: Isadora Cristina de Paula Andrade Almeida
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 10/18095-0 - Study of the eukaryotic translation initiation factor 5A (eIF5A) in mammals
• Grantee: Augusto Ducati Luchessi
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 13/20504-3 - ADJUSTMENT OF POLYAMINE CONTENTS BY MELATONIN AND EFFECTS IN CONTROL OF PROTEIN SYNTHESIS AND DEGRADATION
• Grantee: André Ricardo Gomes de Proença
• Support Opportunities: Scholarships in Brazil - Post-Doctoral