Decay of the stress-induced ligand MICA is controlled by the expression of an alternative 39 untranslated region

Tirtsah Toledano, Alon Vitenshtein, Noam Stern-Ginossar, Einat Seidel, Ofer Mandelboim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Recognition of the human stress-induced ligand MHC class I polypeptide-related sequence A (MICA) by the receptor NKG2D expressed on NK cells leads to NK cell–mediated killing of the target cells. Hence, the expression of MICA must be tightly regulated, and its cell surface expression needs to be quickly downregulated to avoid inappropriate activation of immune cells. In this article, we describe a transcript variant of human MICA that has not yet been studied, which contains a 39 untranslated region of 119 nt instead of 174. We identify its polyadenylation signal and demonstrate that, upon stresses, such as heat shock, butyrate treatment, and some oxidative and DNA-damaging treatments, the balance between the two MICA variants changes in favor of the less stable, longer variant. Mechanistically, we showed that this change is linked to microRNA activity and that poly-ADP ribose polymerase 1 is involved in the induction of the longer variant following stress. Thus, to our knowledge, we identify the first regulatory mechanism of a stress ligand’s decay and also provide one of the first physiological examples for the biological function of a longer 39 untranslated region of a particular gene.

Original languageAmerican English
Pages (from-to)2819-2825
Number of pages7
JournalJournal of Immunology
Issue number8
StatePublished - 15 Apr 2018

Bibliographical note

Funding Information:
This work was supported by the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/European Research Council Grant Agreement Number 320473-BacNK. Additional support came from the Israel Science Foundation, the German-Israeli Foundation for Scientific Research and Development, an Israel Cancer Research Fund professorship grant, a Helmholtz Israel grant, and the Rosetrees Trust (all to O.M.). T.T. was funded in part by the International Volunteers program of the French Ministry of Foreign Affairs and International Development.

Publisher Copyright:
Copyright © 2018 by The American Association of Immunologists, Inc.


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