Research Papers: Immunology:

ADAR1 is vital for B cell lineage development in the mouse bone marrow

Victoria Marcu-Malina, Sanja Goldberg, Einav Vax, Ninette Amariglio, Itamar Goldstein and Gideon Rechavi _

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Oncotarget. 2016; 7:54370-54379. https://doi.org/10.18632/oncotarget.11029

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Victoria Marcu-Malina1, Sanja Goldberg1, Einav Vax1, Ninette Amariglio1,5, Itamar Goldstein1,3,4,* and Gideon Rechavi1,2,4,*

1 Sheba Cancer Research Center, Chaim Sheba Academic Medical Center, Tel Hashomer, Israel

2 Department of Pediatric Hemato-Oncology, Chaim Sheba Academic Medical Center, Tel Hashomer, Israel

3 Rheumatic Diseases Unit, Chaim Sheba Academic Medical Center, Tel Hashomer, Israel

4 Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

5 The Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel

* These authors have contributed equally to this work

Correspondence to:

Gideon Rechavi, email:

Itamar Goldstein, email:

Keywords: RNA editing, ADAR1, B cell, lymphopoiesis, epitranscriptomics, Immunology and Microbiology Section, Immune response, Immunity

Received: July 10, 2016 Accepted: July 23, 2016 Published: August 02, 2016


Adenosine deaminase acting on RNA (ADAR) 1 is the master editor of the transcriptome, catalyzing the conversion of adenosine to inosine (A-to-I). RNA transcripts fold into a variety of secondary structures including long intramolecular RNA duplexes that are the major substrate of ADAR1. Most A-to-I editing sites occur within RNA duplexes formed by complementary pairing of inverted retrotransposable elements interspersed within noncoding regions of transcripts. This catalytic activity of ADAR1 most likely prevents the abnormal activation of cytosolic nucleic acid sensors by self-dsRNAs. Homozygous disruption of mouse Adar is embryonic lethal due to a toxic type-I interferons response and correspondingly biallelic missense mutations in human ADAR1 cause a severe congenital interferonopathy. Here, we report that Cd19-Cre-mediated Adar gene ablation in the mouse causes a significant defect in the final stages of B cell development with an almost complete absence of newly formed immature and CD23+ mature recirculating B cells in the BM. Adar ablation in pre-B cells induced upregulation of typical interferon-stimulated genes (ISGs) and apoptosis upon further maturation. ADAR1 deficiency also inhibited the in vitro, IL-7-mediated, differentiation of BM-derived B cell precursors. In summary, ADAR1 is required, non-redundantly, for normal B lymphopoiesis in the BM and peripheral maintenance.

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