Mammalian DIS3L2 exoribonuclease targets the uridylated precursors of let-7 miRNAs |
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Authors: | Dmytro Ustianenko Dominika Hrossova David Potesil Katerina Chalupnikova Kristyna Hrazdilova Jiri Pachernik Katerina Cetkovska Stjepan Uldrijan Zbynek Zdrahal Stepanka Vanacova |
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Institution: | 1.CEITEC-Central European Institute of Technology, Masaryk University, 625 00, Brno, Czech Republic;2.Department of Experimental Biology, Faculty of Science, Masaryk University, 611 37, Brno, Czech Republic;3.Department of Biology, Faculty of Medicine, Masaryk University, 625 00, Brno, Czech Republic |
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Abstract: | The mechanisms of gene expression regulation by miRNAs have been extensively studied. However, the regulation of miRNA function and decay has long remained enigmatic. Only recently, 3′ uridylation via LIN28A-TUT4/7 has been recognized as an essential component controlling the biogenesis of let-7 miRNAs in stem cells. Although uridylation has been generally implicated in miRNA degradation, the nuclease responsible has remained unknown. Here, we identify the Perlman syndrome-associated protein DIS3L2 as an oligo(U)-binding and processing exoribonuclease that specifically targets uridylated pre-let-7 in vivo. This study establishes DIS3L2 as the missing component of the LIN28-TUT4/7-DIS3L2 pathway required for the repression of let-7 in pluripotent cells. |
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Keywords: | DIS3L2 RNA degradation RNA uridylation let-7 miRNA |
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