Study of the role of elF5A in translation elongation

• Grant number: 10/50044-6
• Support Opportunities: Research Projects - Thematic Grants
• Start date: July 01, 2010
• End date: February 29, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Sandro Roberto Valentini
• Grantee: Sandro Roberto Valentini
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated research grant(s): 13/13225-0 - YEAST 2013: 26th International Conference on Yeast Genetics and Molecular Biology, AR.EXT
• Associated scholarship(s): 15/07728-5 - Analysis of the functional relationship between eIF5A and the transcription factor Hac1 in Saccharomyces cerevisiae, BP.MS; 15/01938-8 - Translation profile of eIF5A dys1-1 hypusination mutant, BP.PD; 14/22067-2 - GC7 hypusination inhibitor specificity and toxicity study using Saccharomyces cerevisiae model, BP.IC; + associated scholarships 14/06270-2 - A specificity and toxicity study of GC7 hypusination inhibitor using Saccharomyces cerevisiae model, BP.IC; 13/10888-9 - Generation and production of single-cysteine mutants of human eIF5A-2 to be used on ribosome binding assays, BP.IC; 13/02233-2 - Study of the role of protein eIF5A in specific tranlation using the model Saccharomyces cerevisiae, BP.MS; 13/06939-7 - Generation of new mutants of eIF5A protein using the strategy of alanine scanning, BP.IC; 12/23890-9 - Biochemical and kinetic study of eIF5A and ribosome direct interaction, using Saccharomyces cerevisiae and human as models, BP.PD; 12/02305-0 - Study of the physical and functional interactions between eIF5A and the translation machinery using Saccharomyces cerevisiae as a model organismo, BP.DD - associated scholarships

Abstract

The translation initiation factor 5A (eIF5A) is highly conserved from archaea to mammals and essential for cell viability. eIF5A is the only protein known to contain the essential amino acid residue hypusine, generated by the enzymes deoxyhypusine synthase and deoxyhypusine hydroxylase. Recent results obtained in our previous study strongly suggest that eIF5A has a role in translation elongation. Therefore, in this project we intend to further investigate the role of eIF5A in translation using the following experimental proposals: 1) study of the functional interaction between eIF5A and translation elongation factors; 2) mapping of eIF5A ribosome binding sites using directed hydroxyl radical probing of rRNA; 3) investigation of a possible role for eIF5A in translation termination; 4) analysis of the functional relationship between eIF5A and tRNAAla; 5) analysis of the association of eIF5A with the secretory pathway and the control of gene expression at the translational level; 6) functional study of the enzyme deoxyhypusine synthase, involved in the first step of eIF5A hypusination; 7) analysis of genetic interactions in large scale involving eIF5A using the Synthetic Genetic Array Analysis - SGA. We expect that the results of these approaches not only unveil additional information on the role played by eIF5A in translation but also determine its involvement in the control of gene expression at the translational level. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ROSSI, DANUZA; BARBOSA, NATALIA M.; GALVAO, FABIO C.; BOLDRIN, PAULO E. G.; HERSHEY, JOHN W. B.; ZANELLI, CLESLEI F.; FRASER, CHRISTOPHER S.; VALENTINI, SANDRO R.. Evidence for a Negative Cooperativity between eIF5A and eEF2 on Binding to the Ribosome. PLoS One, v. 11, n. 4, APR 26 2016. (10/50044-6)

DEMARQUI, FERNANDA MANAIA; SILVA PAIVA, ANA CAROLINA; SANTONI, MARIANA MARCHI; WATANABE, TATIANA FARIA; VALENTINI, SANDRO ROBERTO; ZANELLI, CLESLEI FERNANDO; SETUBAL, JC; SILVA, WM. Polysome-seq as a Measure of Translational Profile from Deoxyhypusine Synthase Mutant in Saccharomyces cerevisiae. ADVANCES IN BIOINFORMATICS AND COMPUTATIONAL BIOLOGY, BSB 2020, v. 12558, p. 12-pg., 2020-01-01. (10/50044-6)

BRANTIS-DE-CARVALHO, CARLOS EDUARDO; MAARIFI, GHIZLANE; GONCALVES BOLDRIN, PAULO EDUARDO; ZANELLI, CLESLEI FERNANDO; NISOLE, SEBASTIEN; CHELBI-ALIX, MOUNIRA K.; VALENTINI, SANDRO ROBERTO. MxA interacts with and is modified by the SUMOylation machinery. Experimental Cell Research, v. 330, n. 1, p. 151-163, JAN 1 2015. (10/50044-6, 03/09497-3)

SILVA PAIVA, ANA CAROLINA; DEMARQUI, FERNANDA MANAIA; SANTONI, MARIANA MARCHI; VALENTINI, SANDRO ROBERTO; ZANELLI, CLESLEI FERNANDO; STADLER, PF; WALTER, MEMT; HERNANDEZ-ROSALES, M; BRIGIDO, MM. Hypusine Plays a Role in the Translation of Short mRNAs and Mediates the Polyamine and Autophagy Pathways in Saccharomyces Cerevisiae. ADVANCES IN BIOINFORMATICS AND COMPUTATIONAL BIOLOGY, BSB 2021, v. 13063, p. 11-pg., 2021-01-01. (10/50044-6)