Mammalian DIS3L2 exoribonuclease targets the uridylated precursors of let-7 miRNAs
- Dmytro Ustianenko1,
- Dominika Hrossova1,
- David Potesil1,
- Katerina Chalupnikova1,
- Kristyna Hrazdilova1,
- Jiri Pachernik2,
- Katerina Cetkovska3,
- Stjepan Uldrijan3,
- Zbynek Zdrahal1 and
- Stepanka Vanacova1,4
- 1CEITEC-Central European Institute of Technology, Masaryk University, 625 00, Brno, Czech Republic
- 2Department of Experimental Biology, Faculty of Science, Masaryk University, 611 37, Brno, Czech Republic
- 3Department of Biology, Faculty of Medicine, Masaryk University, 625 00, Brno, Czech Republic
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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Footnotes
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↵4 Corresponding author
E-mail vanacova{at}chemi.muni.cz
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Freely available online through the RNA Open Access option.
- Received May 8, 2013.
- Accepted August 27, 2013.
This article, published in RNA, is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.
