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

Publication date: 3 April 2018
Source:Cell Reports, Volume 23, Issue 1
Author(s): Shalom Hillel Roth, Miri Danan-Gotthold, Meirav Ben-Izhak, Gideon Rechavi, Cyrille J. Cohen, Yoram Louzoun, Erez Y. Levanon
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.

Graphical abstract

Teaser

Roth et al. show that SLE patients have elevated RNA editing, a process that modifies an RNA sequence from the sequence encoded in the genome. This is manifested as both increased numbers and various altered coding sequences, which may promote autoimmune progression by increasing autoantigenic load.


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