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

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  • Zbigniew Warkocki
  • Pawel S. Krawczyk
  • Dorota Adamska
  • Krystian Bijata
  • Jose L. Garcia-Perez
  • Andrzej Dziembowski

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Original languageEnglish
Pages (from-to)1537-1548.E29
Number of pages41
JournalCell
Volume174
Issue number6
Early online date16 Aug 2018
DOIs
Publication statusPublished - 6 Sep 2018

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.

    Research areas

  • HIGH-FREQUENCY RETROTRANSPOSITION, HUMAN L1 RETROTRANSPOSITION, MESSENGER-RNA, NONCODING RNAS, REVERSE TRANSCRIPTION, SURVEILLANCE PATHWAY, TRIMERIC STRUCTURE, CYTOPLASMIC RNA, CULTURED-CELLS, DEGRADATION

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