title: Uridylation by TUT4 and TUT7 marks mRNA for degradation.
abstract: Uridylation occurs pervasively on mRNAs, yet its mechanism and significance remain unknown. By applying TAIL-seq, we identify TUT4 and TUT7 (TUT4/7), also known as ZCCHC11 and ZCCHC6, respectively, as mRNA uridylation enzymes. Uridylation readily occurs on deadenylated mRNAs in cells. Consistently, purified TUT4/7 selectively recognize and uridylate RNAs with short A-tails (less than ∼ 25 nt) in vitro. PABPC1 antagonizes uridylation of polyadenylated mRNAs, contributing to the specificity for short A-tails. In cells depleted of TUT4/7, the vast majority of mRNAs lose the oligo-U-tails, and their half-lives are extended. Suppression of mRNA decay factors leads to the accumulation of oligo-uridylated mRNAs. In line with this, microRNA induces uridylation of its targets, and TUT4/7 are required for enhanced decay of microRNA targets. Our study explains the mechanism underlying selective uridylation of deadenylated mRNAs and demonstrates a fundamental role of oligo-U-tail as a molecular mark for global mRNA decay.
authors.affiliation: Center for RNA Research, Institute for Basic Science, Seoul 151-742, Korea; School of Biological Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Jaechul
authors.initials: J
authors.lastname: Lim
authors.affiliation: Center for RNA Research, Institute for Basic Science, Seoul 151-742, Korea; School of Biological Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Minju
authors.initials: M
authors.lastname: Ha
authors.affiliation: Center for RNA Research, Institute for Basic Science, Seoul 151-742, Korea; School of Biological Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Hyeshik
authors.initials: H
authors.lastname: Chang
authors.affiliation: Center for RNA Research, Institute for Basic Science, Seoul 151-742, Korea; School of Biological Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: S Chul
authors.initials: SC
authors.lastname: Kwon
authors.affiliation: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Dhirendra K
authors.initials: DK
authors.lastname: Simanshu
authors.affiliation: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Dinshaw J
authors.initials: DJ
authors.lastname: Patel
authors.affiliation: Center for RNA Research, Institute for Basic Science, Seoul 151-742, Korea; School of Biological Sciences, Seoul National University, Seoul 151-742, Korea. Electronic address: narrykim@snu.ac.kr.
authors.forename: V Narry
authors.initials: VN
authors.lastname: Kim
mesh_terms: D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D011061:Poly A / Q000378:metabolism; D039102:Poly(A)-Binding Proteins / Q000378:metabolism; D012316:RNA Nucleotidyltransferases / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D014542:Uridine Monophosphate / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D035683:MicroRNAs; D039102:Poly(A)-Binding Proteins; D012333:RNA, Messenger; C511130:TUT4 protein, human; D011061:Poly A; D014542:Uridine Monophosphate; D012316:RNA Nucleotidyltransferases; C576505:TUT7 protein, human