title: Mammalian DIS3L2 exoribonuclease targets the uridylated precursors of let-7 miRNAs.
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.
authors.forename: Dmytro
authors.initials: D
authors.lastname: Ustianenko
authors.forename: Dominika
authors.initials: D
authors.lastname: Hrossova
authors.forename: David
authors.initials: D
authors.lastname: Potesil
authors.forename: Katerina
authors.initials: K
authors.lastname: Chalupnikova
authors.forename: Kristyna
authors.initials: K
authors.lastname: Hrazdilova
authors.forename: Jiri
authors.initials: J
authors.lastname: Pachernik
authors.forename: Katerina
authors.initials: K
authors.lastname: Cetkovska
authors.forename: Stjepan
authors.initials: S
authors.lastname: Uldrijan
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Zdrahal
authors.forename: Stepanka
authors.initials: S
authors.lastname: Vanacova
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000201:enzymology; D005095:Exoribonucleases / Q000502:physiology*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism*; D020871:RNA Stability; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D035683:MicroRNAs; D012322:RNA Precursors; D034741:RNA, Small Interfering; C487931:mirnlet7 microRNA, human; C571454:DIS3L2 protein, human; D005095:Exoribonucleases
keywords: DIS3L2; RNA degradation; RNA uridylation; let-7 miRNA