The Zinc-Finger Antiviral Protein ZAP Inhibits LINE and Alu Retrotransposition

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Long INterspersed Element-1 (LINE-1 or L1) is the only active autonomous retrotransposon in the human genome. L1s comprise ~17% of human DNA and it is estimated that an average human genome has ~80–100 active L1s. L1 moves throughout the genome via a “copy-and-paste” mechanism known as retrotransposition. L1 retrotransposition is known to cause mutations; thus, it stands to reason that the host cell has evolved mechanisms to protect the cell from unabated retrotransposition. Here, we demonstrate that the zinc-finger antiviral protein (ZAP) inhibits the retrotransposition of human L1 and Alu retrotransposons, as well as related retrotransposons from mice and zebrafish. Biochemical and genetic data suggest that ZAP interacts with L1 RNA. Fluorescent microscopy demonstrates that ZAP associates with L1 in cytoplasmic foci that co-localize with stress granule proteins. Mechanistic analyses suggest that ZAP reduces the expression of full-length L1 RNA and the L1-encoded proteins, thereby providing mechanistic insight for how ZAP may restricts retrotransposition. Importantly, these data suggest that ZAP initially may have evolved to combat endogenous retrotransposons and subsequently was co-opted as a viral restriction factor.

Vyšlo v časopise: The Zinc-Finger Antiviral Protein ZAP Inhibits LINE and Alu Retrotransposition. PLoS Genet 11(5): e32767. doi:10.1371/journal.pgen.1005121
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005121

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