Uridylation by TUT4/7 Restricts Retrotransposition of Human LINE-1s

• Zbigniew Warkocki ^[1] ; Paweł S. Krawczyk ^[1] ; Dorota Adamska ^[1]
  1. [1] Polish Academy of Sciences

     Polish Academy of Sciences

     Warszawa, Polonia

     
• Localización: Cell, ISSN 0092-8674, Vol. 174, Nº. 6, 2018, págs. 1537-1548
• Idioma: inglés
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  • LINE-1 retrotransposition is tightly restricted by layers of regulatory control, with epigenetic pathways being the best characterized. Looking at post-transcriptional regulation, we now show that LINE-1 mRNA 3′ ends are pervasively uridylated in various human cellular models and in mouse testes. TUT4 and TUT7 uridyltransferases catalyze the modification and function in cooperation with the helicase/RNPase MOV10 to counteract the RNA chaperone activity of the L1-ORF1p retrotransposon protein. Uridylation potently restricts LINE-1 retrotransposition by a multilayer mechanism depending on differential subcellular localization of the uridyltransferases. We propose that uridine residues added by TUT7 in the cytoplasm inhibit initiation of reverse transcription of LINE-1 mRNAs once they are reimported to the nucleus, whereas uridylation by TUT4, which is enriched in cytoplasmic foci, destabilizes mRNAs. These results provide a model for the post-transcriptional restriction of LINE-1, revealing a key physiological role for TUT4/7-mediated uridylation in maintaining genome stability.