Tryptophanyl-Transfer RNA Synthetase Is Involved in a Negative Feedback Loop Mitigating Interferon-γ-Induced Gene Expression
Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes responsible for linking a transfer RNA (tRNA) with its cognate amino acid present in all the kingdoms of life. Besides their aminoacyl-tRNA synthetase activity, it was described that many of these enzymes can carry out non-canonical functions....
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MDPI AG
2024-01-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/13/2/180 |
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| author | Ikrame Lazar Ido Livneh Aaron Ciechanover Bertrand Fabre |
| author_facet | Ikrame Lazar Ido Livneh Aaron Ciechanover Bertrand Fabre |
| author_sort | Ikrame Lazar |
| collection | DOAJ |
| description | Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes responsible for linking a transfer RNA (tRNA) with its cognate amino acid present in all the kingdoms of life. Besides their aminoacyl-tRNA synthetase activity, it was described that many of these enzymes can carry out non-canonical functions. They were shown to be involved in important biological processes such as metabolism, immunity, development, angiogenesis and tumorigenesis. In the present work, we provide evidence that tryptophanyl-tRNA synthetase might be involved in a negative feedback loop mitigating the expression of certain interferon-γ-induced genes. Mining the available TCGA and Gtex data, we found that <i>WARS</i> was highly expressed in cutaneous melanoma (SKCM) compared to other cancers and is of good prognosis for this particular cancer type. <i>WARS</i> expression correlates with genes involved in antigen processing and presentation but also transcription factors involved in IFN-γ signaling such as <i>STAT1</i>. In addition, WARS was found in complex with STAT1 in A375 cells treated with IFN-γ. Finally, we showed that knocking down WARS expression during IFN-γ stimulation further increases the expression of <i>GBP2</i>, <i>APOL1</i>, <i>ISG15</i>, <i>HLA-A</i> and <i>IDO1</i>. |
| first_indexed | 2024-03-08T09:55:55Z |
| format | Article |
| id | doaj.art-8292f8df401e4660891064cebf465127 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-08T09:55:55Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-8292f8df401e4660891064cebf4651272024-01-29T13:50:35ZengMDPI AGCells2073-44092024-01-0113218010.3390/cells13020180Tryptophanyl-Transfer RNA Synthetase Is Involved in a Negative Feedback Loop Mitigating Interferon-γ-Induced Gene ExpressionIkrame Lazar0Ido Livneh1Aaron Ciechanover2Bertrand Fabre3The Rappaport Technion Integrated Cancer Center (R-TICC) and the Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 3109601, IsraelThe Rappaport Technion Integrated Cancer Center (R-TICC) and the Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 3109601, IsraelThe Rappaport Technion Integrated Cancer Center (R-TICC) and the Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 3109601, IsraelThe Rappaport Technion Integrated Cancer Center (R-TICC) and the Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 3109601, IsraelAminoacyl-tRNA synthetases (aaRSs) are essential enzymes responsible for linking a transfer RNA (tRNA) with its cognate amino acid present in all the kingdoms of life. Besides their aminoacyl-tRNA synthetase activity, it was described that many of these enzymes can carry out non-canonical functions. They were shown to be involved in important biological processes such as metabolism, immunity, development, angiogenesis and tumorigenesis. In the present work, we provide evidence that tryptophanyl-tRNA synthetase might be involved in a negative feedback loop mitigating the expression of certain interferon-γ-induced genes. Mining the available TCGA and Gtex data, we found that <i>WARS</i> was highly expressed in cutaneous melanoma (SKCM) compared to other cancers and is of good prognosis for this particular cancer type. <i>WARS</i> expression correlates with genes involved in antigen processing and presentation but also transcription factors involved in IFN-γ signaling such as <i>STAT1</i>. In addition, WARS was found in complex with STAT1 in A375 cells treated with IFN-γ. Finally, we showed that knocking down WARS expression during IFN-γ stimulation further increases the expression of <i>GBP2</i>, <i>APOL1</i>, <i>ISG15</i>, <i>HLA-A</i> and <i>IDO1</i>.https://www.mdpi.com/2073-4409/13/2/180tryptophanyl-tRNA synthetasemelanomainterferon-γsignal transducer and activator of transcription 1proteomicsmass spectrometry |
| spellingShingle | Ikrame Lazar Ido Livneh Aaron Ciechanover Bertrand Fabre Tryptophanyl-Transfer RNA Synthetase Is Involved in a Negative Feedback Loop Mitigating Interferon-γ-Induced Gene Expression Cells tryptophanyl-tRNA synthetase melanoma interferon-γ signal transducer and activator of transcription 1 proteomics mass spectrometry |
| title | Tryptophanyl-Transfer RNA Synthetase Is Involved in a Negative Feedback Loop Mitigating Interferon-γ-Induced Gene Expression |
| title_full | Tryptophanyl-Transfer RNA Synthetase Is Involved in a Negative Feedback Loop Mitigating Interferon-γ-Induced Gene Expression |
| title_fullStr | Tryptophanyl-Transfer RNA Synthetase Is Involved in a Negative Feedback Loop Mitigating Interferon-γ-Induced Gene Expression |
| title_full_unstemmed | Tryptophanyl-Transfer RNA Synthetase Is Involved in a Negative Feedback Loop Mitigating Interferon-γ-Induced Gene Expression |
| title_short | Tryptophanyl-Transfer RNA Synthetase Is Involved in a Negative Feedback Loop Mitigating Interferon-γ-Induced Gene Expression |
| title_sort | tryptophanyl transfer rna synthetase is involved in a negative feedback loop mitigating interferon γ induced gene expression |
| topic | tryptophanyl-tRNA synthetase melanoma interferon-γ signal transducer and activator of transcription 1 proteomics mass spectrometry |
| url | https://www.mdpi.com/2073-4409/13/2/180 |
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