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

Warkocki, Zbigniew and Krawczyk, Pawel S and Adamska, Dorota and Bijata, Krystian and Garcia-Perez, Jose L and Dziembowski, Andrzej (2018) Uridylation by TUT4/7 Restricts Retrotransposition of Human LINE-1s. Cell . ISSN 0092-8674

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Official URL: https://doi.org/10.1016/j.cell.2018.07.022

Abstract

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.

Item Type:Article
Uncontrolled Keywords:LINE-1, retrotransposition, uridylation, 3' RACE-seq, TUT7, TUT4, MOV10, L1-ORF1p, L1-ORF2p, poly(A)
Subjects:Q Science > QD Chemistry
Q Science > QH Natural history
Q Science > QH Natural history > QH301 Biology
Divisions:Laboratory of RNA Biology and Functional Genomics
ID Code:1568
Deposited By: Dr ZBIGNIEW WARKOCKI
Deposited On:31 Aug 2018 07:19
Last Modified:31 Aug 2018 07:19

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