title: Uridylation of RNA Hairpins by Tailor Confines the Emergence of MicroRNAs in Drosophila.
abstract: Uridylation of RNA species represents an emerging theme in post-transcriptional gene regulation. In the microRNA pathway, such modifications regulate small RNA biogenesis and stability in plants, worms, and mammals. Here, we report Tailor, an uridylyltransferase that is required for the majority of 3' end modifications of microRNAs in Drosophila and predominantly targets precursor hairpins. Uridylation modulates the characteristic two-nucleotide 3' overhang of microRNA hairpins, which regulates processing by Dicer-1 and destabilizes RNA hairpins. Tailor preferentially uridylates mirtron hairpins, thereby impeding the production of non-canonical microRNAs. Mirtron selectivity is explained by primary sequence specificity of Tailor, selecting substrates ending with a 3' guanosine. In contrast to mirtrons, conserved Drosophila precursor microRNAs are significantly depleted in 3' guanosine, thereby escaping regulatory uridylation. Our data support the hypothesis that evolutionary adaptation to Tailor-directed uridylation shapes the nucleotide composition of precursor microRNA 3' ends. Hence, hairpin uridylation may serve as a barrier for the de novo creation of microRNAs in Drosophila.
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), 1030 Vienna, Austria.
authors.forename: Madalena M
authors.initials: MM
authors.lastname: Reimão-Pinto
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), 1030 Vienna, Austria.
authors.forename: Valentina
authors.initials: V
authors.lastname: Ignatova
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), 1030 Vienna, Austria.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Burkard
authors.affiliation: Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsin-Chu 300, Taiwan.
authors.forename: Jui-Hung
authors.initials: JH
authors.lastname: Hung
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), 1030 Vienna, Austria.
authors.forename: Raphael A
authors.initials: RA
authors.lastname: Manzenreither
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), 1030 Vienna, Austria.
authors.forename: Ivica
authors.initials: I
authors.lastname: Sowemimo
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), 1030 Vienna, Austria.
authors.forename: Veronika A
authors.initials: VA
authors.lastname: Herzog
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), 1030 Vienna, Austria.
authors.forename: Brian
authors.initials: B
authors.lastname: Reichholf
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), 1030 Vienna, Austria.
authors.forename: Sara
authors.initials: S
authors.lastname: Fariña-Lopez
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), 1030 Vienna, Austria. Electronic address: stefan.ameres@imba.oeaw.ac.at.
authors.forename: Stefan L
authors.initials: SL
authors.lastname: Ameres
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D005260:Female; D005298:Fertility / Q000235:genetics / Q000502:physiology; D055785:Gene Knockdown Techniques; D017344:Genes, Insect; D008297:Male; D035683:MicroRNAs / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D012316:RNA Nucleotidyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D013379:Substrate Specificity
chemical_list: D029721:Drosophila Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012316:RNA Nucleotidyltransferases; C031687:UTP-RNA uridylyltransferase