Vigilin regulates the expression of the stress-induced ligand MICB by Interacting with Its 5′ Untranslated Region

Orit Berhani, Daphna Nachmani, Rachel Yamin, Dominik Schmiedel, Yotam Bar-On, Ofer Mandelboim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

NK cells are part of the innate immune system, and are able to identify and kill hazardous cells. The discrimination between normal and hazardous cells is possible due to an array of inhibitory and activating receptors. NKG2D is one of the prominent activating receptors expressed by all human NK cells. This receptor binds stress-induced ligands, including human MICA, MICB, and UL16-binding proteins 1-6. The interaction between NKG2D and its ligands facilitates the elimination of cells under cellular stress, such as tumor transformation. However, the mechanisms regulating the expression of these ligands are still not well understood. Under normal conditions, the NKG2D ligands were shown to be posttranscriptionally regulated by cellular micro-RNAs and RNA-binding proteins (RBPs). Thus far, only the 3′ untranslated regions (UTRs) of MICA, MICB, and UL16-binding protein 2 were shown to be regulated by RBPs and microRNAs, usually resulting in their downregulation. In this study we investigated whether MICB expression is controlled by RBPs through its 5′UTR. We used an RNA pull-down assay followed by mass spectrometry and identified vigilin, a ubiquitously expressed multifunctional RNA-binding protein. We demonstrated that vigilin binds and negatively regulates MICB expression through its 5′UTR. Additionally, vigilin downregulation in target cells led to a significant increase in NK cell activation against said target cells. Taken together, we have discovered a novel mode of MICB regulation.

Original languageAmerican English
Pages (from-to)3662-3670
Number of pages9
JournalJournal of Immunology
Volume198
Issue number9
DOIs
StatePublished - 1 May 2017

Bibliographical note

Publisher Copyright:
Copyright © 2017 by The American Association of Immunologists, Inc.

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