Fig. 7: A working model hypothesizing a negative feedback loop between L1 RNA levels and ISG proteins. | Nature Communications

Fig. 7: A working model hypothesizing a negative feedback loop between L1 RNA levels and ISG proteins.

From: The interferon stimulated gene-encoded protein HELZ2 inhibits human LINE-1 retrotransposition and LINE-1 RNA-mediated type I interferon induction

Fig. 7: A working model hypothesizing a negative feedback loop between L1 RNA levels and ISG proteins.The alternative text for this image may have been generated using AI.

L1 RNAs and/or RNPs can be detected by cytoplasmic RNA sensors, which elicit the secretion of type I interferons (IFNs); ORF1p RNA binding might shield L1 RNA from the sensors. IFN-binding to the extracellular IFN cell surface receptors then activates a signaling cascade, which induces the expression of ISGs, including HELZ2, HERC5, and OASL. These ISG proteins appear to inhibit L1 retrotransposition at different steps in the L1 retrotransposition cycle. HELZ2 appears to recognize RNA sequences and/or RNA structures within the L1 5′UTR, independently of ORF1p RNA binding, leading to the degradation of L1 RNA and subsequent blunting of the IFN response.

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