Polyuridylation in Eukaryotes: A 3′-End Modification Regulating RNA Life

In eukaryotes, mRNA polyadenylation is a well-known modification that is essential for many aspects of the protein-coding RNAs life cycle. However, modification of the 3′ terminal nucleotide within various RNA molecules is a general and conserved process that broadly modulates RNA function in all kingdoms of life. Numerous types of modifications have been characterized, which are generally specific for a given type of RNA such as the CCA addition found in tRNAs. In recent years, the addition of nontemplated uridine nucleotides or uridylation has been shown to occur in various types of RNA molecules and in various cellular compartments with significantly different outcomes. Indeed, uridylation is able to alter RNA half-life both in positive and in negative ways, highlighting the importance of the enzymes in charge of performing this modification. The present review aims at summarizing the current knowledge on the various processes leading to RNA 3′-end uridylation and on their potential impacts in various diseases.

[1]  E. Petfalski,et al.  RNA Degradation by the Exosome Is Promoted by a Nuclear Polyadenylation Complex , 2005, Cell.

[2]  Larry Simpson,et al.  A model for RNA editing in kinetoplastid mitochondria: RNA molecules transcribed from maxicircle DNA provide the edited information , 1990, Cell.

[3]  T. Steitz,et al.  Structural biology: A mechanism for all polymerases , 1998, Nature.

[4]  K. Stuart,et al.  Structural basis for UTP specificity of RNA editing TUTases from Trypanosoma brucei , 2005, The EMBO journal.

[5]  T. Jensen,et al.  Exonuclease hDIS3L2 specifies an exosome‐independent 3′‐5′ degradation pathway of human cytoplasmic mRNA , 2013, The EMBO journal.

[6]  B. Séraphin,et al.  Human Dcp2: a catalytically active mRNA decapping enzyme located in specific cytoplasmic structures , 2002, The EMBO journal.

[7]  R. Gregory,et al.  Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in embryonic stem cells , 2009, Nature Structural &Molecular Biology.

[8]  Larry Simpson,et al.  Trypanosome Mitochondrial 3′ Terminal Uridylyl Transferase (TUTase) The Key Enzyme in U-Insertion/Deletion RNA Editing , 2002, Cell.

[9]  R. Gregory,et al.  Trim71 cooperates with microRNAs to repress Cdkn1a expression and promote embryonic stem cell proliferation , 2012, Nature Communications.

[10]  Xuemei Chen,et al.  Methylation Protects miRNAs and siRNAs from a 3′-End Uridylation Activity in Arabidopsis , 2005, Current Biology.

[11]  P. Klaff,et al.  Addition of destabilizing poly (A)-rich sequences to endonuclease cleavage sites during the degradation of chloroplast mRNA. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Georges Martin,et al.  RNA-specific ribonucleotidyl transferases. , 2007, RNA.

[13]  G. Schuster,et al.  The Mechanism of Preferential Degradation of Polyadenylated RNA in the Chloroplast , 1997, The Journal of Biological Chemistry.

[14]  A. Schnaufer,et al.  Identification of novel components of Trypanosoma brucei editosomes. , 2003, RNA.

[15]  R. Aphasizhev,et al.  RET1-Catalyzed Uridylylation Shapes the Mitochondrial Transcriptome in Trypanosoma brucei , 2010, Molecular and Cellular Biology.

[16]  D. Patel,et al.  Uridylation by TUT4 and TUT7 Marks mRNA for Degradation , 2014, Cell.

[17]  R. Parker,et al.  The 3′ to 5′ degradation of yeast mRNAs is a general mechanism for mRNA turnover that requires the SKI2 DEVH box protein and 3′ to 5′ exonucleases of the exosome complex , 1998, The EMBO journal.

[18]  Lan Huang,et al.  Guide RNA-binding complex from mitochondria of trypanosomatids. , 2008, Molecular cell.

[19]  R. Gregory,et al.  A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28-let-7 pathway , 2013, Nature.

[20]  N. Proudfoot,et al.  Adenylation and exosome-mediated degradation of cotranscriptionally cleaved pre-messenger RNA in human cells. , 2006, Molecular cell.

[21]  Achim Schnaufer,et al.  Complex management: RNA editing in trypanosomes. , 2005, Trends in biochemical sciences.

[22]  V. Kim,et al.  TAIL-seq: genome-wide determination of poly(A) tail length and 3' end modifications. , 2014, Molecular cell.

[23]  C. Joo,et al.  TUT4 in Concert with Lin28 Suppresses MicroRNA Biogenesis through Pre-MicroRNA Uridylation , 2009, Cell.

[24]  Peng Wang,et al.  The Drosophila RNA Methyltransferase, DmHen1, Modifies Germline piRNAs and Single-Stranded siRNAs in RISC , 2007, Current Biology.

[25]  Shimyn Slomovic,et al.  Stable PNPase RNAi silencing: its effect on the processing and adenylation of human mitochondrial RNA. , 2007, RNA.

[26]  K. Stuart,et al.  TbMP44 Is Essential for RNA Editing and Structural Integrity of the Editosome in Trypanosoma brucei , 2003, Eukaryotic Cell.

[27]  R. Aphasizhev,et al.  Terminal RNA uridylyltransferases of trypanosomes. , 2008, Biochimica et biophysica acta.

[28]  J. Deragon,et al.  Uridylation prevents 3′ trimming of oligoadenylated mRNAs , 2013, Nucleic acids research.

[29]  E. Kremmer,et al.  Eri1 degrades the stem-loop of oligouridylated histone mRNAs to induce replication-dependent decay , 2012, Nature Structural &Molecular Biology.

[30]  P. Blackshear,et al.  Interactions of CCCH Zinc Finger Proteins with mRNA , 2000, The Journal of Biological Chemistry.

[31]  Dimitrios Iliopoulos,et al.  Lin28A and Lin28B Inhibit let-7 MicroRNA Biogenesis by Distinct Mechanisms , 2011, Cell.

[32]  C. Sander,et al.  A Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing , 2007, Cell.

[33]  C L Hsu,et al.  Yeast cells lacking 5'-->3' exoribonuclease 1 contain mRNA species that are poly(A) deficient and partially lack the 5' cap structure , 1993, Molecular and cellular biology.

[34]  mRNA poly(A) tail, a 3' enhancer of translational initiation. , 1990 .

[35]  C. Higgins,et al.  Polyadenylation Promotes Degradation of 3′-Structured RNA by theEscherichia coli mRNA Degradosome in Vitro * , 1999, The Journal of Biological Chemistry.

[36]  S. Thore,et al.  Functional implications from the Cid1 poly(U) polymerase crystal structure. , 2012, Structure.

[37]  N. Gray,et al.  Regulation of mRNA translation by 5'- and 3'-UTR-binding factors. , 2003, Trends in biochemical sciences.

[38]  Michael T. McManus,et al.  Widespread RNA 3'-end oligouridylation in mammals. , 2012, RNA.

[39]  W. Marzluff,et al.  The histone 3'-terminal stem-loop is necessary for translation in Chinese hamster ovary cells. , 1996, Nucleic acids research.

[40]  T. Toda,et al.  Cid1, a Fission Yeast Protein Required for S-M Checkpoint Control when DNA Polymerase δ or ɛ Is Inactivated , 2000, Molecular and Cellular Biology.

[41]  Xuemei Chen,et al.  Methylation protects microRNAs from an AGO1-associated activity that uridylates 5′ RNA fragments generated by AGO1 cleavage , 2014, Proceedings of the National Academy of Sciences.

[42]  E. Bartnik,et al.  Human mitochondrial RNA turnover caught in flagranti: involvement of hSuv3p helicase in RNA surveillance , 2009, Nucleic acids research.

[43]  A. W. van der Velden,et al.  The role of the 5' untranslated region of an mRNA in translation regulation during development. , 1999, The international journal of biochemistry & cell biology.

[44]  Weifeng Gu,et al.  Rapid tRNA decay can result from lack of nonessential modifications. , 2006, Molecular cell.

[45]  A. Yoshimura,et al.  A novel Zinc finger protein, ZCCHC11, interacts with TIFA and modulates TLR signaling. , 2006, Biochemical and biophysical research communications.

[46]  H. Luecke,et al.  Structure of the mitochondrial editosome-like complex associated TUTase 1 reveals divergent mechanisms of UTP selection and domain organization. , 2010, Journal of molecular biology.

[47]  J. Steitz,et al.  Association of the lupus antigen La with a subset of U6 snRNA molecules. , 1985, Nucleic acids research.

[48]  Marco M. Kessler,et al.  Structure-Function Relationships in the Saccharomyces cerevisiae Poly(A) Polymerase , 1995, The Journal of Biological Chemistry.

[49]  J. Manley.  Messenger RNA polyadenylylation: a universal modification. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[50]  R. Benne,et al.  Major transcript of the frameshifted coxll gene from trypanosome mitochondria contains four nucleotides that are not encoded in the DNA , 1986, Cell.

[51]  Lucas J. T. Kaaij,et al.  Hen1 is required for oocyte development and piRNA stability in zebrafish , 2010, The EMBO journal.

[52]  J. Lykke-Andersen.  Identification of a Human Decapping Complex Associated with hUpf Proteins in Nonsense-Mediated Decay , 2002, Molecular and Cellular Biology.

[53]  F. Allain,et al.  Structural basis of pre-let-7 miRNA recognition by the zinc knuckles of pluripotency factor Lin28 , 2011, Nature Structural &Molecular Biology.

[54]  Larry Simpson,et al.  A tale of two TUTases , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[55]  D. Geiger,et al.  Polyadenylation and Degradation of Human Mitochondrial RNA: the Prokaryotic Past Leaves Its Mark , 2005, Molecular and Cellular Biology.

[56]  Ryan D. Morin,et al.  Application of massively parallel sequencing to microRNA profiling and discovery in human embryonic stem cells. , 2008, Genome research.

[57]  W. Keller,et al.  No end yet to messenger RNA 3′ processing! , 1995, Cell.

[58]  P. Stepien,et al.  RNA turnover in human mitochondria: more questions than answers? , 2010, Biochimica et biophysica acta.

[59]  S. Balasubramanian,et al.  LIN-28 and the poly(U) polymerase PUP-2 regulate let-7 microRNA processing in Caenorhabditis elegans , 2009, Nature Structural &Molecular Biology.

[60]  K. Stuart,et al.  Direct Visualization of Uridylate Deletion In Vitro Suggests a Mechanism for Kinetoplastid RNA Editing , 1996, Cell.

[61]  Bernd-Joachim Benecke,et al.  A highly specific terminal uridylyl transferase modifies the 3'-end of U6 small nuclear RNA , 1998, Nucleic Acids Res..

[62]  C. Mayr,et al.  Widespread Shortening of 3′UTRs by Alternative Cleavage and Polyadenylation Activates Oncogenes in Cancer Cells , 2009, Cell.

[63]  A. J. Carpousis,et al.  Poly(A) polymerase I of Escherichia coli: characterization of the catalytic domain, an RNA binding site and regions for the interaction with proteins involved in mRNA degradation , 1999, Molecular microbiology.

[64]  Béatrice Conne,et al.  The 3′ untranslated region of messenger RNA: A molecular ‘hotspot’ for pathology? , 2000, Nature Medicine.

[65]  T. Mullen,et al.  Degradation of histone mRNA requires oligouridylation followed by decapping and simultaneous degradation of the mRNA both 5' to 3' and 3' to 5'. , 2008, Genes & development.

[66]  M. Deutscher.  Ribonucleases, tRNA nucleotidyltransferase, and the 3' processing of tRNA. , 1990, Progress in nucleic acid research and molecular biology.

[67]  L. Simpson,et al.  Guide RNAs in kinetoplastid mitochondria have a nonencoded 3′ oligo(U) tail involved in recognition of the preedited region , 1990, Cell.

[68]  Xuemei Chen,et al.  Uridylation of miRNAs by HEN1 SUPPRESSOR1 in Arabidopsis , 2012, Current Biology.

[69]  Zhiping Weng,et al.  Target RNA–Directed Trimming and Tailing of Small Silencing RNAs , 2010, Science.

[70]  Elmar Wahle,et al.  Messenger RNA Turnover in Eukaryotes: Pathways and Enzymes , 2004, Critical reviews in biochemistry and molecular biology.

[71]  Jennifer Hesson,et al.  Untemplated Oligoadenylation Promotes Degradation of RISC-Cleaved Transcripts , 2006, Science.

[72]  R. Aphasizhev,et al.  Uridine insertion/deletion editing in trypanosomes: a playground for RNA‐guided information transfer , 2011, Wiley interdisciplinary reviews. RNA.

[73]  R. Gregory,et al.  Molecular Basis for Interaction of let-7 MicroRNAs with Lin28 , 2011, Cell.

[74]  M. Kiledjian,et al.  Functional Link between the Mammalian Exosome and mRNA Decapping , 2001, Cell.

[75]  Roy Parker,et al.  RNA Quality Control in Eukaryotes , 2007, Cell.

[76]  M. Greenberg,et al.  Two distinct destabilizing elements in the c-fos message trigger deadenylation as a first step in rapid mRNA decay. , 1991, Genes & development.

[77]  Xuemei Chen,et al.  Methylation as a Crucial Step in Plant microRNA Biogenesis , 2005, Science.

[78]  W. Keller,et al.  Mutational analysis of mammalian poly(A) polymerase identifies a region for primer binding and catalytic domain, homologous to the family X polymerases, and to other nucleotidyltransferases. , 1996, The EMBO journal.

[79]  C. Norbury,et al.  Decapping is preceded by 3' uridylation in a novel pathway of bulk mRNA turnover. , 2009, Nature structural & molecular biology.

[80]  Hyeshik Chang,et al.  Mono-Uridylation of Pre-MicroRNA as a Key Step in the Biogenesis of Group II let-7 MicroRNAs , 2012, Cell.

[81]  H. Lipshitz,et al.  Spatial and temporal control of RNA stability , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[82]  Xuemei Chen,et al.  The Arabidopsis Nucleotidyl Transferase HESO1 Uridylates Unmethylated Small RNAs to Trigger Their Degradation , 2012, Current Biology.

[83]  R. Gregory,et al.  Lin28-mediated control of let-7 microRNA expression by alternative TUTases Zcchc11 (TUT4) and Zcchc6 (TUT7). , 2012, RNA.

[84]  Vidya Mani,et al.  Deep sequencing of microRNA precursors reveals extensive 3' end modification. , 2011, RNA.

[85]  Reza Salavati,et al.  TbMP57 is a 3' terminal uridylyl transferase (TUTase) of the Trypanosoma brucei editosome. , 2003, Molecular cell.

[86]  M. Kiledjian,et al.  3' Terminal oligo U-tract-mediated stimulation of decapping. , 2007, RNA.

[87]  A. Jacobson,et al.  mRNA poly(A) tail, a 3' enhancer of translational initiation , 1990, Molecular and cellular biology.

[88]  Pedro J. Batista,et al.  CDE-1 Affects Chromosome Segregation through Uridylation of CSR-1-Bound siRNAs , 2009, Cell.

[89]  M. Mörl,et al.  Exchange of regions between bacterial poly(A) polymerase and the CCA-adding enzyme generates altered specificities. , 2004, Molecular cell.

[90]  E. Lund,et al.  Cyclic 2',3'-phosphates and nontemplated nucleotides at the 3' end of spliceosomal U6 small nuclear RNA's. , 1992, Science.

[91]  Pedro J. Batista,et al.  Distinct argonaute-mediated 22G-RNA pathways direct genome surveillance in the C. elegans germline. , 2009, Molecular cell.

[92]  H. Urlaub,et al.  Identification, cloning, and functional analysis of the human U6 snRNA-specific terminal uridylyl transferase. , 2006, RNA.

[93]  Shulan Tian,et al.  Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells , 2007, Science.

[94]  C. Norbury,et al.  The human cytoplasmic RNA terminal U-transferase ZCCHC11 targets histone mRNAs for degradation. , 2011, RNA.

[95]  Pamela J Green,et al.  Uridylation of mature miRNAs and siRNAs by the MUT68 nucleotidyltransferase promotes their degradation in Chlamydomonas , 2010, Proceedings of the National Academy of Sciences.

[96]  Pedro J. Batista,et al.  The Argonaute CSR-1 and Its 22G-RNA Cofactors Are Required for Holocentric Chromosome Segregation , 2009, Cell.

[97]  T. Dunckley,et al.  The DCP2 protein is required for mRNA decapping in Saccharomyces cerevisiae and contains a functional MutT motif , 1999, The EMBO journal.

[98]  E V Koonin,et al.  DNA polymerase beta-like nucleotidyltransferase superfamily: identification of three new families, classification and evolutionary history. , 1999, Nucleic acids research.

[99]  Sara L. Zimmer,et al.  Polyadenylation in Arabidopsis and Chlamydomonas organelles: the input of nucleotidyltransferases, poly(A) polymerases and polynucleotide phosphorylase. , 2009, The Plant journal : for cell and molecular biology.

[100]  N. Wilkie,et al.  Chain extension of ribonucleic acid by enzymes from rat liver cytoplasm. , 1968, The Biochemical journal.

[101]  J. Doudna,et al.  The stem-loop binding protein forms a highly stable and specific complex with the 3' stem-loop of histone mRNAs. , 2001, RNA.

[102]  K. Piller,et al.  Purification of a functional enzymatic editing complex from Trypanosoma brucei mitochondria , 1997, The EMBO journal.

[103]  C. Norbury,et al.  Efficient RNA Polyuridylation by Noncanonical Poly(A) Polymerases , 2007, Molecular and Cellular Biology.

[104]  L. Maquat,et al.  Regulation of cytoplasmic mRNA decay , 2012, Nature Reviews Genetics.

[105]  E. Canellakis.  Incorporation of radioactive uridine-5'-monophosphate into ribonucleic acid by soluble mammalian enzymes. , 1957, Biochimica et Biophysica Acta.

[106]  W. Marzluff,et al.  The stem-loop structure at the 3' end of histone mRNA is necessary and sufficient for regulation of histone mRNA stability , 1987, Molecular and cellular biology.

[107]  Yahua Chen,et al.  Effect of 3' terminal adenylic acid residue on the uridylation of human small RNAs in vitro and in frog oocytes. , 2000, RNA.

[108]  Haiwei Song,et al.  The enzymes and control of eukaryotic mRNA turnover , 2004, Nature Structural &Molecular Biology.

[109]  R Parker,et al.  A turnover pathway for both stable and unstable mRNAs in yeast: evidence for a requirement for deadenylation. , 1993, Genes & development.

[110]  H. Bayley,et al.  Detection of 3'-end RNA uridylation with a protein nanopore. , 2014, ACS nano.

[111]  Henriette M. Kurth,et al.  2'-O-methylation stabilizes Piwi-associated small RNAs and ensures DNA elimination in Tetrahymena. , 2009, RNA.

[112]  Roger Y Tsien,et al.  Control of mammalian translation by mRNA structure near caps. , 2006, RNA.

[113]  P. Golik,et al.  The exoribonuclease Dis3L2 defines a novel eukaryotic RNA degradation pathway , 2013, The EMBO journal.

[114]  P. Blackshear,et al.  Feedback Inhibition of Macrophage Tumor Necrosis Factor-α Production by Tristetraprolin , 1998 .

[115]  J. Abelson.  RNA processing and the intervening sequence problem. , 1979, Annual review of biochemistry.

[116]  M. Osley.  The regulation of histone synthesis in the cell cycle. , 1991, Annual review of biochemistry.

[117]  J. Neilson,et al.  Zcchc11-dependent uridylation of microRNA directs cytokine expression , 2009, Nature Cell Biology.

[118]  Lan Huang,et al.  Pentatricopeptide repeat proteins stimulate mRNA adenylation/uridylation to activate mitochondrial translation in trypanosomes. , 2011, Molecular cell.