title: Selective Suppression of the Splicing-Mediated MicroRNA Pathway by the Terminal Uridyltransferase Tailor.
abstract: Several terminal uridyltransferases (TUTases) are known to modulate small RNA biogenesis and/or function via diverse mechanisms. Here, we demonstrate that Drosophila splicing-derived pre-miRNAs (mirtrons) are efficiently modified by the previously uncharacterized TUTase, Tailor. Tailor is necessary and sufficient for mirtron hairpin uridylation, and this modification inhibits mirtron biogenesis. Genome-wide analyses demonstrate that mirtrons are dominant Tailor substrates, and three features contribute to substrate specificity. First, reprogramming experiments show Tailor preferentially identifies splicing-derived miRNAs. Second, in vitro tests indicate Tailor prefers substrate hairpins over mature miRNAs. Third, Tailor exhibits sequence preference for 3'-terminal AG, a defining mirtron characteristic. Our work supports the notion that Tailor preferentially suppresses biogenesis of mirtrons, an evolutionarily adventitious pre-miRNA substrate class. Moreover, we detect preferential activity of Tailor on 3'-G canonical pre-miRNAs, and specific depletion of such loci from the pool of conserved miRNAs. Thus, Tailor activity may have had collateral impact on shaping populations of canonical miRNAs.
authors.affiliation: Sloan-Kettering Institute, Department of Developmental Biology, 1275 York Avenue, Box 252, New York, NY 10065, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Bortolamiol-Becet
authors.affiliation: Sloan-Kettering Institute, Department of Developmental Biology, 1275 York Avenue, Box 252, New York, NY 10065, USA.
authors.forename: Fuqu
authors.initials: F
authors.lastname: Hu
authors.affiliation: Sloan-Kettering Institute, Department of Developmental Biology, 1275 York Avenue, Box 252, New York, NY 10065, USA; Biochemistry Cell and Molecular Biology Program, Weill Graduate School of Medical Sciences, Cornell University, New York, NY 10065, USA.
authors.forename: David
authors.initials: D
authors.lastname: Jee
authors.affiliation: Sloan-Kettering Institute, Department of Developmental Biology, 1275 York Avenue, Box 252, New York, NY 10065, USA.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Wen
authors.affiliation: Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, Singapore 117604, Singapore; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 639798, Singapore.
authors.forename: Katsutomo
authors.initials: K
authors.lastname: Okamura
authors.affiliation: Sloan-Kettering Institute, Department of Developmental Biology, 1275 York Avenue, Box 252, New York, NY 10065, USA; Biochemistry Cell and Molecular Biology Program, Weill Graduate School of Medical Sciences, Cornell University, New York, NY 10065, USA.
authors.forename: Ching-Jung
authors.initials: CJ
authors.lastname: Lin
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
authors.forename: Stefan L
authors.initials: SL
authors.lastname: Ameres
authors.affiliation: Sloan-Kettering Institute, Department of Developmental Biology, 1275 York Avenue, Box 252, New York, NY 10065, USA. Electronic address: laie@mskcc.org.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Lai
mesh_terms: D000818:Animals; D001483:Base Sequence; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D005260:Female; D055785:Gene Knockdown Techniques; D017344:Genes, Insect; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D010053:Ovary / Q000378:metabolism; D012316:RNA Nucleotidyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D012326:RNA Splicing; D013379:Substrate Specificity
chemical_list: D029721:Drosophila Proteins; D035683:MicroRNAs; D012316:RNA Nucleotidyltransferases; C031687:UTP-RNA uridylyltransferase