西亚试剂：LysRS Serves as a Key Signaling Molecule in the Immune Resp

发布时间：2026-01-22

LysRS Serves as a Key Signaling Molecule in the Immune Response by Regulating Gene Expression

Nurit Yannay-Cohen1, 5, Irit Carmi-Levy1, 5, Gillian Kay1, Christopher Maolin Yang2, Jung Min Han3, D. Michael Kemeny2, Sunghoon Kim3, Hovav Nechushtan4, ,   and Ehud Razin1, ,

1 Department of Biochemistry, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel
2 Department of Microbiology and Immunology Program, Life Science Institute, National University of Singapore 117456, Republic of Singapore
3 Center for Medicinal Protein Network and Systems Biology, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea
4 Oncology Department, Hadassah Hebrew University Medical Center, P.O. Box 12272, Jerusalem 91120, Israel

Lysyl-tRNA synthetase (LysRS) was found to produce diadenosine tetraphosphate (Ap4A) in vitro more than two decades ago. Here, we used LysRS silencing in mast cells in combination with transfected normal and mutated LysRS to demonstrate in vivo the critical role played by LysRS in the production of Ap4A in response to immunological challenge. Upon such challenge, LysRS was phosphorylated on serine 207 in a MAPK-dependent manner, released from the multisynthetase complex, and translocated into the nucleus. We previously demonstrated that LysRS forms a complex with MITF and its repressor Hint-1, which is released from the complex by its binding to Ap4A, enabling MITF to transcribe its target genes. Here, silencing LysRS led to reduced Ap4A production in immunologically activated cells, which resulted in a lower level of MITF inducible genes. Our data demonstrate that specific LysRS serine 207 phosphorylation regulates Ap4A production in immunologically stimulated mast cells, thus implying that LysRS is a key mediator in gene regulation.

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