Key result
Widespread loss of adenosine-to-inosine editing of Alu RNAs occurs in multiple sclerosis, and unedited Alu RNAs potently activate proinflammatory IFN and NF-κB responses via RIG-I and TLR3.
Why the study?
The mechanisms underlying increases in double-stranded endogenous Alu RNAs and resulting interferon responses in relapsing-remitting multiple sclerosis were obscure.
Answers are grounded in this paper and cite their sources.
Identifies a potential proinflammatory pathway in MS; hypothesis-generating and requires clinical validation before therapeutic consideration.
Sensors that detect dsRNA stimulate IFN responses as a defense against viral infection. IFN responses are also well documented in a variety of human autoimmune diseases, including relapsing-remitting multiple sclerosis (MS), in which increased IFN responses result from increased levels of double-stranded endogenous Alu RNAs. Mechanisms underlying increases in double-stranded Alu RNAs in MS are obscure. We find widespread loss of adenosine-to-inosine editing of Alu RNAs in MS. Unedited Alu RNAs are potent activators of both IFN and NF-κB responses via the dsRNA sensors, RIG-I, and TLR3. Minor editing of highly active Alu elements abrogates the ability to activate both transcriptional responses. Thus, adenosine-to-inosine editing may also represent an important defense against autoimmune diseases such as MS.
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Tossberg et al. (2020) studied Relapsing-remitting multiple sclerosis (MS). Unedited Alu double-stranded RNAs was evaluated on IFN and NF-κB responses. Widespread loss of adenosine-to-inosine editing of Alu RNAs occurs in multiple sclerosis, and unedited Alu RNAs potently activate proinflammatory IFN and NF-κB responses via RIG-I and TLR3.
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