Acute LINE-1 transcription remodels the molecular landscape of human fibroblasts

In primary human IMR-90 fibroblasts, transient activation of the retrotransposon LINE-1 reshapes molecular networks across multiple cellular layers, according to a recent preprint. Researchers used transcriptomics, proteomics, and secretomics to measure the systems-level effects of acute human L1Hs overexpression in these healthy cells. They found that transient L1Hs expression induced widespread remodeling across the transcriptome, proteome, and secretome. The expression altered pathways tied to cell cycle control and interferon signaling. When evaluating multiple independent L1 elements, the team observed both shared and distinct cellular responses to acute expression. Overall, acute L1 transcription triggered coordinated molecular changes that reached beyond canonical retrotransposition pathways rather than simply mimicking senescence or antiviral responses.