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PMID: 29617672 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Increased RNA Editing May Provide a Source for Autoantigens in Systemic Lupus Erythematosus.

Cell reports ·Vol. 23 ·No. 1 ·2018-00-03 ·Pages 50-57

Roth SH, Danan-Gotthold M, Ben-Izhak M, Rechavi G, Cohen CJ, Louzoun Y, Levanon EY

Abstract

RNA-editing mechanisms, which induce nucleotide substitution in the RNA, increase transcript and protein diversities. Editing dysregulation has been shown to lead to grave outcomes, and transcriptome-wide aberrant RNA editing has been found in tumors. However, little is known about the involvement of editing in other diseases. Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease characterized by a loss of tolerance for autoantigens from various tissues and the production of multiple autoantibodies. Here, we show that blood samples from individuals with SLE have abnormally high levels of RNA editing, some of which affect proteins and potentially generate novel autoantigens. We suggest that elevated RNA editing, either by ADARs or APOBECs, may be involved in the pathophysiology of SLE, as well as in other autoimmune diseases, by generating or increasing the autoantigen load, a key requisite for the progression of autoimmunity.

Keywords
A-to-I editing ADAR APOBEC3 C-to-U editing RNA editing SLE autoimmune disease immune tolerance neo-autoantigens systemic lupus erythematosus
MeSH Terms
APOBEC Deaminases Adenosine Deaminase/metabolism Autoantigens/genetics Cytidine Deaminase Cytosine Deaminase/metabolism Humans Immune Tolerance/genetics Lupus Erythematosus, Systemic/genetics,immunology RNA Editing RNA-Binding Proteins/metabolism
Chemicals
Autoantigens RNA-Binding Proteins Cytosine Deaminase ADAR protein, human Adenosine Deaminase APOBEC Deaminases APOBEC3 protein, human Cytidine Deaminase
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Roth Shalom Hillel
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 5290002, Israel.
Danan-Gotthold Miri
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 5290002, Israel.
Ben-Izhak Meirav
Department of Mathematics, Bar-Ilan University, Ramat Gan 5290002, Israel; The Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat Gan 5290002, Israel.
Rechavi Gideon
Cancer Research Center and the Wohl Institute for Translational Medicine, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.
Cohen Cyrille J
Laboratory of Tumor Immunology and Immunotherapy, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 5290002, Israel.
Louzoun Yoram
Department of Mathematics, Bar-Ilan University, Ramat Gan 5290002, Israel; The Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat Gan 5290002, Israel.
Levanon Erez Y
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 5290002, Israel.
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Article Info
Journal
Cell reports
Abbr.
Cell Rep
ISSN
2211-1247
DOI
10.1016/j.celrep.2018.03.036
Published
2018-00-03
Pages
50-57
Language
English
Region
United States
NLM ID
101573691
PMCID
PMC5905401
Subset
IM
Grants
European Research Council · 311257 · International
External Links
PubMed source DOI: 10.1016/j.celrep.2018.03.036 PMC Full Text View journal details
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