Macrophages fuse distant gene transcripts to build immune proteins
Mouse macrophages join RNA transcripts from separate chromosomes to produce working proteins that regulate inflammation, according to a study published in Nature on 5 March 2026. Venezia, Kane, and colleagues used long-read RNA sequencing and chromatin conformation capture to show that inflammation triggers interchromosomal DNA interactions that bring distant genes close enough for their transcripts to splice together. One chimera fuses gasdermin D with a segment of Tmem106a translated out of frame to create a protein called GSDMD-TMEM106A. After inflammasome priming, this chimeric protein moves to the plasma membrane, where it binds canonical GSDMD fragments and accelerates pore formation and IL-1β release.
Regulated fusion of transcripts from distant loci can produce functional proteins that balance host defense against immunopathology during sepsis.
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