Tryptophanyl-Transfer RNA Synthetase Is Involved in a Negative Feedback Loop Mitigating Interferon-γ-Induced Gene Expression.

Cells

The Rappaport Technion Integrated Cancer Center (R-TICC) and the Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 3109601, Israel.

Published: January 2024

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 was highly expressed in cutaneous melanoma (SKCM) compared to other cancers and is of good prognosis for this particular cancer type. expression correlates with genes involved in antigen processing and presentation but also transcription factors involved in IFN-γ signaling such as . 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 , , , and .

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10813977PMC
http://dx.doi.org/10.3390/cells13020180DOI Listing

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