title: TUT-DIS3L2 is a mammalian surveillance pathway for aberrant structured non-coding RNAs.
abstract: Uridylation of various cellular RNA species at the 3' end has been generally linked to RNA degradation. In mammals, uridylated pre-let-7 miRNAs and mRNAs are targeted by the 3' to 5' exoribonuclease DIS3L2. Mutations in DIS3L2 have been associated with Perlman syndrome and with Wilms tumor susceptibility. Using in vivo cross-linking and immunoprecipitation (CLIP) method, we discovered the DIS3L2-dependent cytoplasmic uridylome of human cells. We found a broad spectrum of uridylated RNAs including rRNAs, snRNAs, snoRNAs, tRNAs, vault, 7SL, Y RNAs, mRNAs, lncRNAs, and transcripts from pseudogenes. The unifying features of most of these identified RNAs are aberrant processing and the presence of stable secondary structures. Most importantly, we demonstrate that uridylation mediates DIS3L2 degradation of short RNA polymerase II-derived RNAs. Our findings establish the role of DIS3L2 and oligouridylation as the cytoplasmic quality control for highly structured ncRNAs.
authors.affiliation: CEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Dmytro
authors.initials: D
authors.lastname: Ustianenko
authors.affiliation: CEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Josef
authors.initials: J
authors.lastname: Pasulka
authors.affiliation: CEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Feketova
authors.affiliation: CEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Lukas
authors.initials: L
authors.lastname: Bednarik
authors.affiliation: CEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic.|National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Brno, Czech Republic.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Zigackova
authors.affiliation: CEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Andrea
authors.initials: A
authors.lastname: Fortova
authors.affiliation: Biozentrum, University of Basel and Swiss Institute of Bioinformatics, Basel, Switzerland.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Zavolan
authors.affiliation: CEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic stepanka.vanacova@ceitec.muni.cz.
authors.forename: Stepanka
authors.identifier: 0000-0001-8807-0684
authors.initials: S
authors.lastname: Vanacova
mesh_terms: D002460:Cell Line; D005095:Exoribonucleases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D009713:Nucleotidyltransferases / Q000378:metabolism; D022661:RNA, Untranslated / Q000378:metabolism*
chemical_list: D022661:RNA, Untranslated; D009713:Nucleotidyltransferases; C571454:DIS3L2 protein, human; D005095:Exoribonucleases
keywords: DIS3L2; RNA surveillance; TSSa; ncRNAs; uridylation