The Deficiency of Hypusinated eIF5A Decreases the Putrescine/Spermidine Ratio and Inhibits +1 Programmed Ribosomal Frameshifting during the Translation of Ty1 Retrotransposon in <i>Saccharomyces cerevisiae</i>
Programmed ribosomal frameshifting (PRF) exists in all branches of life that regulate gene expression at the translational level. The eukaryotic translation initiation factor 5A (eIF5A) is a highly conserved protein essential in all eukaryotes. It is identified initially as an initiation factor and...
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MDPI AG
2024-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/3/1766 |
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| author | Yu Xiao Ruanlin Wang Xiaxia Han Wei Wang Aihua Liang |
| author_facet | Yu Xiao Ruanlin Wang Xiaxia Han Wei Wang Aihua Liang |
| author_sort | Yu Xiao |
| collection | DOAJ |
| description | Programmed ribosomal frameshifting (PRF) exists in all branches of life that regulate gene expression at the translational level. The eukaryotic translation initiation factor 5A (eIF5A) is a highly conserved protein essential in all eukaryotes. It is identified initially as an initiation factor and functions broadly in translation elongation and termination. The hypusination of eIF5A is specifically required for +1 PRF at the shifty site derived from the <i>ornithine decarboxylase antizyme 1</i> (<i>OAZ1</i>) in <i>Saccharomyces cerevisiae</i>. However, whether the regulation of +1 PRF by yeast eIF5A is universal remains unknown. Here, we found that Sc-eIF5A depletion decreased the putrescine/spermidine ratio. The re-introduction of Sc-eIF5A in yeast eIF5A mutants recovered the putrescine/spermidine ratio. In addition, the Sc-eIF5A depletion decreases +1 PRF during the decoding of <i>Ty1</i> retrotransposon mRNA, but has no effect on −1 PRF during the decoding of <i>L-A</i> virus mRNA. The re-introduction of Sc-eIF5A in yeast eIF5A mutants restored the +1 PRF rate of Ty1. The inhibition of the hypusine modification of yeast eIF5A by GC7 treatment or by mutating the hypusination site Lys to Arg caused decreases of +1 PRF rates in the <i>Ty1</i> retrotransposon. Furthermore, mutational studies of the <i>Ty1</i> frameshifting element support a model where the efficient removal of ribosomal subunits at the first <i>Ty1</i> frame 0 stop codon is required for the frameshifting of trailing ribosomes. This dependency is likely due to the unique position of the frame 0 stop codon distance from the slippery sequence of <i>Ty1</i>. The results showed that eIF5A is a <i>trans</i>-regulator of +1 PRF for <i>Ty1</i> retrotransposon and could function universally in yeast. |
| first_indexed | 2024-03-08T03:54:29Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T03:54:29Z |
| publishDate | 2024-02-01 |
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| spelling | doaj.art-4288bd0fcfbc40c48af7d42572f6c7de2024-02-09T15:14:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-02-01253176610.3390/ijms25031766The Deficiency of Hypusinated eIF5A Decreases the Putrescine/Spermidine Ratio and Inhibits +1 Programmed Ribosomal Frameshifting during the Translation of Ty1 Retrotransposon in <i>Saccharomyces cerevisiae</i>Yu Xiao0Ruanlin Wang1Xiaxia Han2Wei Wang3Aihua Liang4Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, ChinaKey Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, ChinaKey Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, ChinaKey Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, ChinaKey Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, ChinaProgrammed ribosomal frameshifting (PRF) exists in all branches of life that regulate gene expression at the translational level. The eukaryotic translation initiation factor 5A (eIF5A) is a highly conserved protein essential in all eukaryotes. It is identified initially as an initiation factor and functions broadly in translation elongation and termination. The hypusination of eIF5A is specifically required for +1 PRF at the shifty site derived from the <i>ornithine decarboxylase antizyme 1</i> (<i>OAZ1</i>) in <i>Saccharomyces cerevisiae</i>. However, whether the regulation of +1 PRF by yeast eIF5A is universal remains unknown. Here, we found that Sc-eIF5A depletion decreased the putrescine/spermidine ratio. The re-introduction of Sc-eIF5A in yeast eIF5A mutants recovered the putrescine/spermidine ratio. In addition, the Sc-eIF5A depletion decreases +1 PRF during the decoding of <i>Ty1</i> retrotransposon mRNA, but has no effect on −1 PRF during the decoding of <i>L-A</i> virus mRNA. The re-introduction of Sc-eIF5A in yeast eIF5A mutants restored the +1 PRF rate of Ty1. The inhibition of the hypusine modification of yeast eIF5A by GC7 treatment or by mutating the hypusination site Lys to Arg caused decreases of +1 PRF rates in the <i>Ty1</i> retrotransposon. Furthermore, mutational studies of the <i>Ty1</i> frameshifting element support a model where the efficient removal of ribosomal subunits at the first <i>Ty1</i> frame 0 stop codon is required for the frameshifting of trailing ribosomes. This dependency is likely due to the unique position of the frame 0 stop codon distance from the slippery sequence of <i>Ty1</i>. The results showed that eIF5A is a <i>trans</i>-regulator of +1 PRF for <i>Ty1</i> retrotransposon and could function universally in yeast.https://www.mdpi.com/1422-0067/25/3/1766<i>Saccharomyces cerevisiae</i>programmed ribosomal frameshiftingeIF5ATy1 retrotransposon |
| spellingShingle | Yu Xiao Ruanlin Wang Xiaxia Han Wei Wang Aihua Liang The Deficiency of Hypusinated eIF5A Decreases the Putrescine/Spermidine Ratio and Inhibits +1 Programmed Ribosomal Frameshifting during the Translation of Ty1 Retrotransposon in <i>Saccharomyces cerevisiae</i> International Journal of Molecular Sciences <i>Saccharomyces cerevisiae</i> programmed ribosomal frameshifting eIF5A Ty1 retrotransposon |
| title | The Deficiency of Hypusinated eIF5A Decreases the Putrescine/Spermidine Ratio and Inhibits +1 Programmed Ribosomal Frameshifting during the Translation of Ty1 Retrotransposon in <i>Saccharomyces cerevisiae</i> |
| title_full | The Deficiency of Hypusinated eIF5A Decreases the Putrescine/Spermidine Ratio and Inhibits +1 Programmed Ribosomal Frameshifting during the Translation of Ty1 Retrotransposon in <i>Saccharomyces cerevisiae</i> |
| title_fullStr | The Deficiency of Hypusinated eIF5A Decreases the Putrescine/Spermidine Ratio and Inhibits +1 Programmed Ribosomal Frameshifting during the Translation of Ty1 Retrotransposon in <i>Saccharomyces cerevisiae</i> |
| title_full_unstemmed | The Deficiency of Hypusinated eIF5A Decreases the Putrescine/Spermidine Ratio and Inhibits +1 Programmed Ribosomal Frameshifting during the Translation of Ty1 Retrotransposon in <i>Saccharomyces cerevisiae</i> |
| title_short | The Deficiency of Hypusinated eIF5A Decreases the Putrescine/Spermidine Ratio and Inhibits +1 Programmed Ribosomal Frameshifting during the Translation of Ty1 Retrotransposon in <i>Saccharomyces cerevisiae</i> |
| title_sort | deficiency of hypusinated eif5a decreases the putrescine spermidine ratio and inhibits 1 programmed ribosomal frameshifting during the translation of ty1 retrotransposon in i saccharomyces cerevisiae i |
| topic | <i>Saccharomyces cerevisiae</i> programmed ribosomal frameshifting eIF5A Ty1 retrotransposon |
| url | https://www.mdpi.com/1422-0067/25/3/1766 |
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