title: Molecular basis for cytoplasmic RNA surveillance by uridylation-triggered decay in Drosophila.
abstract: The posttranscriptional addition of nucleotides to the 3' end of RNA regulates the maturation, function, and stability of RNA species in all domains of life. Here, we show that in flies, 3' terminal RNA uridylation triggers the processive, 3'-to-5' exoribonucleolytic decay via the RNase II/R enzyme CG16940, a homolog of the human Perlman syndrome exoribonuclease Dis3l2. Together with the TUTase Tailor, dmDis3l2 forms the cytoplasmic, terminal RNA uridylation-mediated processing (TRUMP) complex that functionally cooperates in the degradation of structured RNA RNA immunoprecipitation and high-throughput sequencing reveals a variety of TRUMP complex substrates, including abundant non-coding RNA, such as 5S rRNA, tRNA, snRNA, snoRNA, and the essential RNase MRP Based on genetic and biochemical evidence, we propose a key function of the TRUMP complex in the cytoplasmic quality control of RNA polymerase III transcripts. Together with high-throughput biochemical characterization of dmDis3l2 and bacterial RNase R, our results imply a conserved molecular function of RNase II/R enzymes as "readers" of destabilizing posttranscriptional marks-uridylation in eukaryotes and adenylation in prokaryotes-that play important roles in RNA surveillance.
authors.affiliation: Institute of Molecular Biotechnology, IMBA, Vienna Biocenter Campus (VBC), Vienna, Austria.
authors.forename: Madalena M
authors.initials: MM
authors.lastname: Reimão-Pinto
authors.affiliation: Institute of Molecular Biotechnology, IMBA, Vienna Biocenter Campus (VBC), Vienna, Austria.
authors.forename: Raphael A
authors.initials: RA
authors.lastname: Manzenreither
authors.affiliation: Institute of Molecular Biotechnology, IMBA, Vienna Biocenter Campus (VBC), Vienna, Austria.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Burkard
authors.affiliation: Department of Biochemistry, University of Zurich, Zurich, Switzerland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Sledz
authors.affiliation: Department of Biochemistry, University of Zurich, Zurich, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Jinek
authors.affiliation: Institute of Molecular Biotechnology, IMBA, Vienna Biocenter Campus (VBC), Vienna, Austria.
authors.forename: Karl
authors.identifier: 0000-0002-3392-9946
authors.initials: K
authors.lastname: Mechtler
authors.affiliation: Institute of Molecular Biotechnology, IMBA, Vienna Biocenter Campus (VBC), Vienna, Austria stefan.ameres@imba.oeaw.ac.at.
authors.forename: Stefan L
authors.identifier: 0000-0002-8248-3098
authors.initials: SL
authors.lastname: Ameres
mesh_terms: D000818:Animals; D002460:Cell Line; D003593:Cytoplasm / Q000737:chemistry* / Q000378:metabolism*; D004330:Drosophila / Q000378:metabolism*; D005095:Exoribonucleases / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability
chemical_list: D005095:Exoribonucleases; C022535:exoribonuclease II
keywords: Dis3l2; RNA decay; RNA surveillance; exoribonuclease; uridylation