RNA-binding proteins regulate the expression of the immune activating ligand MICB

Daphna Nachmani, Tony Gutschner, Adi Reches, Sven Diederichs, Ofer Mandelboim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


The recognition of stress-induced ligands by the activating receptor NKG2D expressed on cytotoxic lymphocytes is crucial for the prevention and containment of various diseases and is also one of the best-studied examples of how danger is sensed by the immune system. Still, however, the mechanisms leading to the expression of the NKG2D ligands are far from being completely understood. Here, we use an unbiased and systematic RNA pull-down approach combined with mass spectrometry to identify six RNA-binding proteins (RBPs) that bind and regulate the expression of MICB, one of the major stress-induced ligands of NKG2D. We further demonstrate that at least two of the identified RBPs function during genotoxic stress. Our data provide insights into stress recognition and hopefully open new therapeutic venues.

Original languageAmerican English
Article number4186
JournalNature Communications
StatePublished - 13 Jun 2014

Bibliographical note

Funding Information:
This study was supported by the MOST-DKFZ Cooperation programme (Ca-135, to O.M. and S.D.) and funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement number 320473-BacNK. Further support came from the GIF foundation, from the Lewis family foundation, the ICRF professorship grant, the Israeli Science Foundation and the Rosetrees Trust (all to O.M.). O.M. is a Crown Professor of Molecular Immunology. D.N. is supported by the Adams Fellowship Programme of the Israel Academy of Sciences and Humanities. Research in the Diederichs Lab is supported by the Helmholtz Society (VH-NG-504), the Excellence Cluster CellNetworks, and the Virtual Helmholtz Institute for Resistance in Leukaemia. The authors thank Yoav Livneh for fruitful discussions.


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