What is it about?

RNAs can fold into double-stranded structures capable of inducing interferon results. Cells need a mechanism to turn-off any interferon responses triggered by self doubled stranded RNAs, yet one that still allows a response against viral double-stranded RNAs. Humans achieve this outcome by recognizing a repeat sequence unique to humans. The sequence adopts a left-handed Z-RNA conformation (rather than the usual right-handed A-RNA form) when proteins that drive the interferon response bind. The altered RNA structure is recognized by an RNA editing enzyme called ADAR that can destabilize the double-stranded RNA and end the interferon response against self.

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Why is it important?

The mechanism prevents immune responses against self that could lead to autoimmune diseases, yet it allows immune responses against viruses.


The sequences marking human double-stranded RNAs arose from retroviral elements called Alu elements that spread through the human genome by a copy and paste process . These sequences were originally a threat to survival of the species as they often inserted into active genes. However over time, the retroelements were tamed. They now serve to defend the host by providing a way to identify human transcripts as self.

Alan Herbert

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This page is a summary of: To “Z” or not to “Z”: Z-RNA, self-recognition, and the MDA5 helicase, PLoS Genetics, May 2021, PLOS, DOI: 10.1371/journal.pgen.1009513.
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