The Broad-Spectrum Antiviral Protein ZAP Restricts Human Retrotransposition

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Retrotransposons are mobile DNA elements that duplicate themselves by a "copy and paste" mechanism using an RNA intermediate. They are insertional mutagens that have had profound effects on genome evolution, fostering DNA deletions, insertions and rearrangements, and altering gene expression. LINE-1 retrotransposons occupy 17% of human DNA, although it is believed that only about 100 remain competent for retrotransposition in any individual. The cell has evolved defenses restricting retrotransposition, involving in some cases interferon-stimulated genes (ISGs) that are part of the innate immune system that protects the cell from viral infections. We screened a panel of ISGs and found several to strongly limit retrotransposition in a cell culture assay. Our investigations increase understanding of how ZAP, an important restriction factor against positive- and negative-strand RNA and some DNA viruses, also interacts with human retrotransposons to prevent genome mutation. Microscopy and immunoprecipitation show a close association of ZAP protein with the L1 ribonucleoprotein particle, as well as MOV10, an RNA helicase that also inhibits retrotransposons. A detailed examination of the ZAP protein interactome reveals many other ISGs that directly bind ZAP, and suggests new directions for exploring the mechanisms of ZAP-mediated anti-retroelement activity.

Vyšlo v časopise: The Broad-Spectrum Antiviral Protein ZAP Restricts Human Retrotransposition. PLoS Genet 11(5): e32767. doi:10.1371/journal.pgen.1005252
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005252

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