Hypusine Plays a Role in the Translation of Short mRNAs and Mediates the Polyamine and Autophagy Pathways in Saccharomyces Cerevisiae
Resumo
The cell highly regulates the translational process aiming to maintain cellular stability and viability for mechanisms at the transcriptional, translational, or metabolic level, such as the control of transcripts forwarded for translation or autophagy. The translation elongation factor 5A (eIF5A) is evolutionarily conserved and essential in eukaryotic cells. eIF5A undergoes a post-translational modification, called hypusination, which has two enzymatic steps. The first stage, catalyzed by the deoxyhypusine synthase, occurs in a spermidine-dependent manner. Spermidine is a polyamine in which intracellular imbalance can affect some cellular processes. Studies show that this modification is fundamental to the role of eIF5A in the cell, assisting in the translation of a subset of mRNA. We analyzed transcriptional and translational profiles of the deoxyhypusine synthase mutant (dys1-1) in Saccharomyces cerevisiae. From Polysome-seq, our results showed that the lack of hypusination leads to the impairment on the translation of short ORFs, that code ribosomal mitochondrial proteins. From both profiles, the expression of genes and transcription factors of the polyamine pathway, which needs strict cell control, was altered. Besides, the inhibition of hypusination by GC7 showed an increase in the protein level of two autophagy proteins, Atg1 and Atg33, the latter is specific to mitophagy. In response to the metabolic problems caused by non-hypusination, the cell can respond with mitophagy and macroautophagy to maintain cell stability.
Palavras-chave:
Deoxyhypusine synthase, eIF5A, GC7
Referências
Abelson, J.N., Simon, M.I., Guthrie, C., Fink, G.R.: Guide to yeast genetics and molecular biology 194, 1–863 (1991). https://doi.org/10.2307/3760517
Annette, K., et al.: Modification of eukaryotic initiation factor 5A from plasmodium vivax by a truncated deoxyhypusine synthase from plasmodium falciparum: an enzyme with dual enzymatic properties. Bioorg. Med. Chem. 15(18), 6200–6207 (2007). https://doi.org/10.1016/J.BMC.2007.06.026
Benjamini, Y., Yekutieli, D.: The control of the false discovery rate in multiple testing under dependency. Ann. Stat. 29, 1165–1188 (2001). https://doi.org/10.1214/aos/1013699998
Caplan, A.J., Cyr, D.M., Douglas, M.G.: YDJ1p facilitates polypeptide translocation across different intracellular membranes by a conserved mechanism. Cell 71(7), 1143–1155 (1992). https://doi.org/10.1016/S0092-8674(05)80063-7
Chattopadhyay, M.K., Chen, W., Poy, G., Cam, M., Stiles, D., Tabor, H.: Microarray studies on the genes responsive to the addition of spermidine or spermine to a saccharomyces cerevisiae spermidine synthase mutant. Yeast 26(10), 531–544 (2009). https://doi.org/10.1002/yea.1703
Chen, K.Y., Liu, A.Y.: Biochemistry and function of hypusine formation on eukaryotic initiation factor 5A. NeuroSignals 6, 105–109 (1997). https://doi.org/10.1159/000109115
Chen, Y., Klionsky, D.J.: The regulation of autophagy - unanswered questions (2011). https://doi.org/10.1242/jcs.064576
Demarqui, F.M., Paiva, A.C.S., Santoni, MMi., Watanabe, T.F., Valentini, S.R., Zanelli, C.F.: Polysome-seq as a measure of translational profile from deoxyhypusine synthase mutant in saccharomyces cerevisiae. In: BSB 2020. LNCS, vol. 12558, pp. 168–179. Springer, Cham (2020). https://doi.org/10.1007/978-3-030-65775-8_16
Dever, T.E., Dinman, J.D., Green, R.: Translation Elongation and Recoding in Eukaryotes. Cold Spring Harb. Perspect Biol. 10, a032649 (2018). https://doi.org/10.1101/cshperspect.a032649
Engel, S.R., et al.: The reference genome sequence of saccharomyces cerevisiae: then and now. G3: Genes Genomes Genet 4(3), 389–398 (2014). https://doi.org/10.1534/g3.113.008995
Galvão, F.C., Rossi, D., Silveira, W.D.S., Valentini, S.R., Zanelli, C.F.: The deoxyhypusine synthase mutant dys1-1 reveals the association of eIF5A and Asc1 with cell wall integrity. PLOS ONE 8(4), e60140 (2013). https://doi.org/10.1371/JOURNAL.PONE.0060140
Gamble, C.E., Brule, C.E., Dean, K.M., Fields, S., Grayhack, E.J.: Adjacent codons act in concert to modulate translation efficiency in yeast. Cell 166(3), 679–690 (2016). https://doi.org/10.1016/j.cell.2016.05.070
Heyer, E.E., Moore, M.J.: Redefining the translational status of 80s monosomes. Cell 164(4), 757–769 (2016). https://doi.org/10.1016/j.cell.2016.01.003, https://www.sciencedirect.com/science/article/pii/S0092867416000040
Hurowitz, E.H., Brown, P.O.: Genome-wide analysis of mRNA lengths in saccharomyces cerevisiae. Genome Biol. 5(1), 3889–3894 (2003). https://doi.org/10.1186/gb-2003-5-1-r2
Ingolia, N.T., Ghaemmaghami, S., Newman, J.R., Weissman, J.S.: Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling. Science 324(5924), 218–223 (2009). https://doi.org/10.1126/science.1168978
Ivanov, I.P., et al.: Polyamine control of translation elongation regulates start site selection on antizyme inhibitor mRNA via ribosome queuing. Mol. Cell 70(2), 254-264.e6 (2018). https://doi.org/10.1016/j.molcel.2018.03.015
KJ, L., TD, S.: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods (San Diego, Calif.) 25(4), 402–408 (2001). https://doi.org/10.1006/METH.2001.1262
Lubas, M., et al.: eIF 5A is required for autophagy by mediating ATG 3 translation. EMBO Rep. 19(6), e46072 (2018). https://doi.org/10.15252/embr.201846072
Madeo, F., Tobias, E., Sabrina, B., Christoph, R., Guido, K.: Spermidine: a novel autophagy inducer and longevity elixir. Autophagy 6(1), 160–162 (2010). https://doi.org/10.4161/AUTO.6.1.10600
Melis, N., et al.: Targeting eIF5A hypusination prevents anoxic cell death through mitochondrial silencing and improves kidney transplant outcome. J. Am. Soc. Nephrol. 28(3), 811–822 (2017). https://doi.org/10.1681/ASN.2016010012
Miller-Fleming, L., Olin-Sandoval, V., Campbell, K., Ralser, M.: Remaining mysteries of molecular biology: the role of polyamines in the cell (2015). https://doi.org/10.1016/j.jmb.2015.06.020
Oertlin, C., Lorent, J., Murie, C., Furic, L., Topisirovic,I., Larsson, O.: Generally applicable transcriptome-wide analysis of translation using anota2seq. Nucleic Acids Res. 47(12), e70 (2019). https://doi.org/10.1093/nar/gkz223
Oliver H, L., Nira J, R., A Lewis, F., Rose J, R.: Protein measurement with the folin phenol reagent. J. Biol. Chem. 193(1), 265–275 (1951)
Park, M.H., Nishimura, K., Zanelli, C.F., Valentini, S.R.: Functional significance of eIF5A and its hypusine modification in eukaryotes. Amino Acids 38(2), 491–500 (2010). https://doi.org/10.1007/s00726-009-0408-7
Pegg, A.E.: Functions of polyamines in mammals (2016). https://doi.org/10.1074/jbc.R116.731661
Puleston, D.J., et al.: Polyamines and eIF5A hypusination modulate mitochondrial respiration and macrophage activation. Cell Metab. 30(2), 352-363.e8 (2019). https://doi.org/10.1016/j.cmet.2019.05.003
Rossi, D., Kuroshu, R., Zanelli, C.F., Valentini, S.R.: eIF5A and EF-P: two unique translation factors are now traveling the same road (2014). https://doi.org/10.1002/wrna.1211
Schnier, J., Schwelberger, H.G., Smit-McBride, Z., Kang, H.A., Hershey, J.W.: Translation initiation factor 5A and its hypusine modification are essential for cell viability in the yeast Saccharomyces cerevisiae. Mol. Cell. Biol. (1991). https://doi.org/10.1128/MCB.11.6.3105
Schuller, A.P., Green, R.: Roadblocks and resolutions in eukaryotic translation. Nat. Rev. Mol. Cell Biol. 19, 526–541 (2018). https://doi.org/10.1038/s41580-018-0011-4
Schuller, A.P., Wu, C.C.C., Dever, T.E., Buskirk, A.R., Green, R.: eIF5A functions globally in translation elongation and termination. Mol. Cell 66(2), 194-205.e5 (2017). https://doi.org/10.1016/j.molcel.2017.03.003
Shi, X.P., Yin, K.C., Ahern, J., Davis, L.J., Stern, A.M., Waxman, L.: Effects of N1-guanyl-1,7-diaminoheptane, an inhibitor of deoxyhypusine synthase, on the growth of tumorigenic cell lines in culture. Biochim. et Biophys. Acta - Mol. Cell Res. 1310(1), 119–126 (1996). https://doi.org/10.1016/0167-4889(95)00165-4
Shirokikh, N.E., Preiss, T.: Translation initiation by cap-dependent ribosome recruitment: Recent insights and open questions. Wiley Interdisc. Rev. RNA 9(4),(2018). https://doi.org/10.1002/wrna.1473
Sina, G., et al.: Global analysis of protein expression in yeast. Nature 425(6959), 737–741 (2003). https://doi.org/10.1038/NATURE02046
Thompson, M.K., Rojas-Duran, M.F., Gangaramani, P., Gilbert, W.V.: The ribosomal protein Asc1/RACK1 is required for efficient translation of short mRNAs. eLife 5, e11154 (2016). https://doi.org/10.7554/eLife.11154
Weinberg, D.E., Shah, P., Eichhorn, S.W., Hussmann, J.A., Plotkin, J.B., Bartel, D.P.: Improved ribosome-footprint and mRNA measurements provide insights into dynamics and regulation of yeast translation. Cell Rep. 14(7), 1787–1799 (2016). https://doi.org/10.1016/j.celrep.2016.01.043
Yi, C., et al.: Formation of a Snf1-Mec1-Atg1 module on mitochondria governs energy deprivation-induced autophagy by regulating mitochondrial respiration. Dev. Cell 41(1), 59-71.e4 (2017). https://doi.org/10.1016/j.devcel.2017.03.007
Annette, K., et al.: Modification of eukaryotic initiation factor 5A from plasmodium vivax by a truncated deoxyhypusine synthase from plasmodium falciparum: an enzyme with dual enzymatic properties. Bioorg. Med. Chem. 15(18), 6200–6207 (2007). https://doi.org/10.1016/J.BMC.2007.06.026
Benjamini, Y., Yekutieli, D.: The control of the false discovery rate in multiple testing under dependency. Ann. Stat. 29, 1165–1188 (2001). https://doi.org/10.1214/aos/1013699998
Caplan, A.J., Cyr, D.M., Douglas, M.G.: YDJ1p facilitates polypeptide translocation across different intracellular membranes by a conserved mechanism. Cell 71(7), 1143–1155 (1992). https://doi.org/10.1016/S0092-8674(05)80063-7
Chattopadhyay, M.K., Chen, W., Poy, G., Cam, M., Stiles, D., Tabor, H.: Microarray studies on the genes responsive to the addition of spermidine or spermine to a saccharomyces cerevisiae spermidine synthase mutant. Yeast 26(10), 531–544 (2009). https://doi.org/10.1002/yea.1703
Chen, K.Y., Liu, A.Y.: Biochemistry and function of hypusine formation on eukaryotic initiation factor 5A. NeuroSignals 6, 105–109 (1997). https://doi.org/10.1159/000109115
Chen, Y., Klionsky, D.J.: The regulation of autophagy - unanswered questions (2011). https://doi.org/10.1242/jcs.064576
Demarqui, F.M., Paiva, A.C.S., Santoni, MMi., Watanabe, T.F., Valentini, S.R., Zanelli, C.F.: Polysome-seq as a measure of translational profile from deoxyhypusine synthase mutant in saccharomyces cerevisiae. In: BSB 2020. LNCS, vol. 12558, pp. 168–179. Springer, Cham (2020). https://doi.org/10.1007/978-3-030-65775-8_16
Dever, T.E., Dinman, J.D., Green, R.: Translation Elongation and Recoding in Eukaryotes. Cold Spring Harb. Perspect Biol. 10, a032649 (2018). https://doi.org/10.1101/cshperspect.a032649
Engel, S.R., et al.: The reference genome sequence of saccharomyces cerevisiae: then and now. G3: Genes Genomes Genet 4(3), 389–398 (2014). https://doi.org/10.1534/g3.113.008995
Galvão, F.C., Rossi, D., Silveira, W.D.S., Valentini, S.R., Zanelli, C.F.: The deoxyhypusine synthase mutant dys1-1 reveals the association of eIF5A and Asc1 with cell wall integrity. PLOS ONE 8(4), e60140 (2013). https://doi.org/10.1371/JOURNAL.PONE.0060140
Gamble, C.E., Brule, C.E., Dean, K.M., Fields, S., Grayhack, E.J.: Adjacent codons act in concert to modulate translation efficiency in yeast. Cell 166(3), 679–690 (2016). https://doi.org/10.1016/j.cell.2016.05.070
Heyer, E.E., Moore, M.J.: Redefining the translational status of 80s monosomes. Cell 164(4), 757–769 (2016). https://doi.org/10.1016/j.cell.2016.01.003, https://www.sciencedirect.com/science/article/pii/S0092867416000040
Hurowitz, E.H., Brown, P.O.: Genome-wide analysis of mRNA lengths in saccharomyces cerevisiae. Genome Biol. 5(1), 3889–3894 (2003). https://doi.org/10.1186/gb-2003-5-1-r2
Ingolia, N.T., Ghaemmaghami, S., Newman, J.R., Weissman, J.S.: Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling. Science 324(5924), 218–223 (2009). https://doi.org/10.1126/science.1168978
Ivanov, I.P., et al.: Polyamine control of translation elongation regulates start site selection on antizyme inhibitor mRNA via ribosome queuing. Mol. Cell 70(2), 254-264.e6 (2018). https://doi.org/10.1016/j.molcel.2018.03.015
KJ, L., TD, S.: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods (San Diego, Calif.) 25(4), 402–408 (2001). https://doi.org/10.1006/METH.2001.1262
Lubas, M., et al.: eIF 5A is required for autophagy by mediating ATG 3 translation. EMBO Rep. 19(6), e46072 (2018). https://doi.org/10.15252/embr.201846072
Madeo, F., Tobias, E., Sabrina, B., Christoph, R., Guido, K.: Spermidine: a novel autophagy inducer and longevity elixir. Autophagy 6(1), 160–162 (2010). https://doi.org/10.4161/AUTO.6.1.10600
Melis, N., et al.: Targeting eIF5A hypusination prevents anoxic cell death through mitochondrial silencing and improves kidney transplant outcome. J. Am. Soc. Nephrol. 28(3), 811–822 (2017). https://doi.org/10.1681/ASN.2016010012
Miller-Fleming, L., Olin-Sandoval, V., Campbell, K., Ralser, M.: Remaining mysteries of molecular biology: the role of polyamines in the cell (2015). https://doi.org/10.1016/j.jmb.2015.06.020
Oertlin, C., Lorent, J., Murie, C., Furic, L., Topisirovic,I., Larsson, O.: Generally applicable transcriptome-wide analysis of translation using anota2seq. Nucleic Acids Res. 47(12), e70 (2019). https://doi.org/10.1093/nar/gkz223
Oliver H, L., Nira J, R., A Lewis, F., Rose J, R.: Protein measurement with the folin phenol reagent. J. Biol. Chem. 193(1), 265–275 (1951)
Park, M.H., Nishimura, K., Zanelli, C.F., Valentini, S.R.: Functional significance of eIF5A and its hypusine modification in eukaryotes. Amino Acids 38(2), 491–500 (2010). https://doi.org/10.1007/s00726-009-0408-7
Pegg, A.E.: Functions of polyamines in mammals (2016). https://doi.org/10.1074/jbc.R116.731661
Puleston, D.J., et al.: Polyamines and eIF5A hypusination modulate mitochondrial respiration and macrophage activation. Cell Metab. 30(2), 352-363.e8 (2019). https://doi.org/10.1016/j.cmet.2019.05.003
Rossi, D., Kuroshu, R., Zanelli, C.F., Valentini, S.R.: eIF5A and EF-P: two unique translation factors are now traveling the same road (2014). https://doi.org/10.1002/wrna.1211
Schnier, J., Schwelberger, H.G., Smit-McBride, Z., Kang, H.A., Hershey, J.W.: Translation initiation factor 5A and its hypusine modification are essential for cell viability in the yeast Saccharomyces cerevisiae. Mol. Cell. Biol. (1991). https://doi.org/10.1128/MCB.11.6.3105
Schuller, A.P., Green, R.: Roadblocks and resolutions in eukaryotic translation. Nat. Rev. Mol. Cell Biol. 19, 526–541 (2018). https://doi.org/10.1038/s41580-018-0011-4
Schuller, A.P., Wu, C.C.C., Dever, T.E., Buskirk, A.R., Green, R.: eIF5A functions globally in translation elongation and termination. Mol. Cell 66(2), 194-205.e5 (2017). https://doi.org/10.1016/j.molcel.2017.03.003
Shi, X.P., Yin, K.C., Ahern, J., Davis, L.J., Stern, A.M., Waxman, L.: Effects of N1-guanyl-1,7-diaminoheptane, an inhibitor of deoxyhypusine synthase, on the growth of tumorigenic cell lines in culture. Biochim. et Biophys. Acta - Mol. Cell Res. 1310(1), 119–126 (1996). https://doi.org/10.1016/0167-4889(95)00165-4
Shirokikh, N.E., Preiss, T.: Translation initiation by cap-dependent ribosome recruitment: Recent insights and open questions. Wiley Interdisc. Rev. RNA 9(4),(2018). https://doi.org/10.1002/wrna.1473
Sina, G., et al.: Global analysis of protein expression in yeast. Nature 425(6959), 737–741 (2003). https://doi.org/10.1038/NATURE02046
Thompson, M.K., Rojas-Duran, M.F., Gangaramani, P., Gilbert, W.V.: The ribosomal protein Asc1/RACK1 is required for efficient translation of short mRNAs. eLife 5, e11154 (2016). https://doi.org/10.7554/eLife.11154
Weinberg, D.E., Shah, P., Eichhorn, S.W., Hussmann, J.A., Plotkin, J.B., Bartel, D.P.: Improved ribosome-footprint and mRNA measurements provide insights into dynamics and regulation of yeast translation. Cell Rep. 14(7), 1787–1799 (2016). https://doi.org/10.1016/j.celrep.2016.01.043
Yi, C., et al.: Formation of a Snf1-Mec1-Atg1 module on mitochondria governs energy deprivation-induced autophagy by regulating mitochondrial respiration. Dev. Cell 41(1), 59-71.e4 (2017). https://doi.org/10.1016/j.devcel.2017.03.007
Publicado
22/11/2021
Como Citar
PAIVA, Ana Carolina Silva; DEMARQUI, Fernanda Manaia; SANTONI, Mariana Marchi; VALENTINI, Sandro Roberto; ZANELLI, Cleslei Fernando.
Hypusine Plays a Role in the Translation of Short mRNAs and Mediates the Polyamine and Autophagy Pathways in Saccharomyces Cerevisiae. In: SIMPÓSIO BRASILEIRO DE BIOINFORMÁTICA (BSB), 14. , 2021, Online.
Anais [...].
Porto Alegre: Sociedade Brasileira de Computação,
2021
.
p. 15-25.
ISSN 2316-1248.
