An RNA Splicing System that Excises Transposons from Animal mRNAs

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Publicado en:bioRxiv (Feb 17, 2025)
Autor principal: Long-Wen, Zhao
Otros Autores: Nardone, Christopher, Paulo, Joao A, Elledge, Stephen, Kennedy, Scott
Publicado:
Cold Spring Harbor Laboratory Press
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Acceso en línea:Citation/Abstract
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Resumen:All genomes harbor mobile genetic parasites called transposable elements (TEs). Here we describe a system, which we term SOS splicing, that protects C. elegans and human genes from DNA transposon-mediated disruption by excising these TEs from host mRNAs. SOS splicing, which operates independently of the spliceosome, is a pattern recognition system triggered by base-pairing of inverted terminal repeat elements, which are a defining feature of the DNA transposons. We identify three factors required for SOS splicing in both C. elegans and human cells; AKAP17A, which binds TE-containing mRNAs; the RNA ligase RTCB; and CAAP1, which bridges RTCB and AKAP17A, allowing RTCB to ligate mRNA fragments generated by TE excision. We propose that SOS splicing is a novel, conserved, and RNA structure-directed mode of mRNA splicing and that one function of SOS splicing is to genetically buffer animals from the deleterious effects of TE-mediated gene perturbation.Competing Interest StatementS.J.E. is a founder of TSCAN Therapeutics, MAZE Therapeutics, ImmuneID, and Mirimus, serves on the scientific advisory boards of Homology Medicines, ImmuneID, MAZE Therapeutics, X-Chem, and TSCAN Therapeutics, and is an advisor for MPM Capital. Other authors declare no competing interests.
ISSN:2692-8205
DOI:10.1101/2025.02.14.638102
Fuente:Biological Science Database