AI Article Synopsis
- Innate immune signaling is crucial for eliminating pathogens and damaged cells, but must be precisely controlled to prevent too much inflammation or autoimmunity.* -
- The study reveals that alternative splicing from transposable elements plays a significant role in regulating immune signaling in human cells, particularly impacting immune genes like the type I interferon receptor IFNAR2.* -
- The research shows that a transposon-derived version of IFNAR2, which inhibits interferon signaling more effectively than the standard version, is more prevalent in various tissues and can impact responses in cells infected with SARS-CoV-2.*
Article Abstract
Innate immune signaling is essential for clearing pathogens and damaged cells and must be tightly regulated to avoid excessive inflammation or autoimmunity. Here, we found that the alternative splicing of exons derived from transposable elements is a key mechanism controlling immune signaling in human cells. By analyzing long-read transcriptome datasets, we identified numerous transposon exonization events predicted to generate functional protein variants of immune genes, including the type I interferon receptor IFNAR2. We demonstrated that the transposon-derived isoform of IFNAR2 is more highly expressed than the canonical isoform in almost all tissues and functions as a decoy receptor that potently inhibits interferon signaling, including in cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our findings uncover a primate-specific axis controlling interferon signaling and show how a transposon exonization event can be co-opted for immune regulation.
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| http://dx.doi.org/10.1016/j.cell.2024.11.016 | DOI Listing |
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