Summary: A class of enzymes that transfers nucleotidyl residues. EC 2.7.7.

Top Publications

  1. Hyde S, Rao B, Eckenroth B, Jackman J, Doublié S. Structural studies of a bacterial tRNA(HIS) guanylyltransferase (Thg1)-like protein, with nucleotide in the activation and nucleotidyl transfer sites. PLoS ONE. 2013;8:e67465 pubmed publisher
    ..The BtTLP structural data, combined with kinetic analysis of selected variants, provide new insight into the role of key residues in the activation step. ..
  2. Lapointe C, Wickens M. The nucleic acid-binding domain and translational repression activity of a Xenopus terminal uridylyl transferase. J Biol Chem. 2013;288:20723-33 pubmed publisher
    ..Our data reveal key aspects of how XTUT7 adds uridines to RNAs, highlight the role of the basic region, illustrate that XTUT7 can repress translation, and identify an amino acid important for uridine specificity...
  3. Wiltrout M, Walker G. The DNA polymerase activity of Saccharomyces cerevisiae Rev1 is biologically significant. Genetics. 2011;187:21-35 pubmed publisher
    ..Furthermore, Pol ?, but not Pol ?, also contributes to 4-NQO resistance. These results show that Rev1's catalytic activity is important in vivo when the cell has to cope with specific DNA lesions, such as N(2)-dG. ..
  4. Jimeno González S, Haaning L, Malagon F, Jensen T. The yeast 5'-3' exonuclease Rat1p functions during transcription elongation by RNA polymerase II. Mol Cell. 2010;37:580-7 pubmed publisher
    ..Our data suggest that Rat1p serves to terminate RNAPII molecules engaged in the production of uncapped RNA, regardless of their position on the gene locus. ..
  5. Wojtaszek J, Lee C, D Souza S, Minesinger B, Kim H, D Andrea A, et al. Structural basis of Rev1-mediated assembly of a quaternary vertebrate translesion polymerase complex consisting of Rev1, heterodimeric polymerase (Pol) ?, and Pol ?. J Biol Chem. 2012;287:33836-46 pubmed
  6. Abad M, Rao B, Jackman J. Template-dependent 3'-5' nucleotide addition is a shared feature of tRNAHis guanylyltransferase enzymes from multiple domains of life. Proc Natl Acad Sci U S A. 2010;107:674-9 pubmed publisher
  7. Yang T, Echols M, Martin A, Bar Peled M. Identification and characterization of a strict and a promiscuous N-acetylglucosamine-1-P uridylyltransferase in Arabidopsis. Biochem J. 2010;430:275-84 pubmed publisher
    ..The ability of GlcNAc1pUT-2 to utilize three different substrates may provide further understanding as to why biological systems have plasticity. ..
  8. Luong P, Kinch L, Brautigam C, Grishin N, Tomchick D, Orth K. Kinetic and structural insights into the mechanism of AMPylation by VopS Fic domain. J Biol Chem. 2010;285:20155-63 pubmed publisher
    ..Discovery of a ternary reaction mechanism along with structural insight provides critical groundwork for future studies for the family of AMPylators that modify hydroxyl-containing residues with AMP...
  9. Placido A, Sieber F, Gobert A, Gallerani R, Giegé P, Maréchal Drouard L. Plant mitochondria use two pathways for the biogenesis of tRNAHis. Nucleic Acids Res. 2010;38:7711-7 pubmed publisher
    ..This shows that a previously unreported tRNA(His) guanylyltransferase activity is present in plant mitochondria. ..

More Information


  1. Phillips L, Sale J. The Werner's Syndrome protein collaborates with REV1 to promote replication fork progression on damaged DNA. DNA Repair (Amst). 2010;9:1064-72 pubmed publisher
  2. Pedrolli D, Nakanishi S, Barile M, Mansurova M, Carmona E, Lux A, et al. The antibiotics roseoflavin and 8-demethyl-8-amino-riboflavin from Streptomyces davawensis are metabolized by human flavokinase and human FAD synthetase. Biochem Pharmacol. 2011;82:1853-9 pubmed publisher
    ..RoF, but not AF, was found to inhibit human flavokinase. In summary, we suggest that AF has a lower toxic potential and may be better suited as a lead structure to develop antimicrobial compounds. ..
  3. Gao D, Wu J, Wu Y, Du F, Aroh C, Yan N, et al. Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses. Science. 2013;341:903-6 pubmed publisher
    ..These results indicate that cGAS is an innate immune sensor of HIV and other retroviruses. ..
  4. Wang H, Yu C, Zhu Z, Yu X. Overexpression in tobacco of a tomato GMPase gene improves tolerance to both low and high temperature stress by enhancing antioxidation capacity. Plant Cell Rep. 2011;30:1029-40 pubmed publisher
    ..In conclusion, the overexpression of GMPase increased the content of AsA, thereby leading to the increase in tolerance to temperature stress in transgenic plants. ..
  5. Torchetti E, Brizio C, Colella M, Galluccio M, Giancaspero T, Indiveri C, et al. Mitochondrial localization of human FAD synthetase isoform 1. Mitochondrion. 2010;10:263-73 pubmed publisher
    ..Immunofluorescence confocal microscopy performed on BHK-21 and Caco-2 cell lines transiently expressing the two human isoforms, definitively confirmed that hFADS1, but not hFADS2, localizes in mitochondria. ..
  6. Sharma S, Hicks J, Chute C, Brennan J, Ahn J, Glover T, et al. REV1 and polymerase ? facilitate homologous recombination repair. Nucleic Acids Res. 2012;40:682-91 pubmed publisher
    ..Thus, the REV1/Pol? complex maintains genomic stability by directly participating in DSB repair in addition to the canonical TLS pathway. ..
  7. Diamant N, Hendel A, Vered I, Carell T, Reissner T, de Wind N, et al. DNA damage bypass operates in the S and G2 phases of the cell cycle and exhibits differential mutagenicity. Nucleic Acids Res. 2012;40:170-80 pubmed publisher
    ..Such a mechanism may function to maintain efficient replication, which can progress despite the presence of DNA lesions, with TLS lagging behind and patching regions of discontinuity. ..
  8. Smith B, Jackman J. Kinetic analysis of 3'-5' nucleotide addition catalyzed by eukaryotic tRNA(His) guanylyltransferase. Biochemistry. 2012;51:453-65 pubmed publisher
    ..These data provide a foundation for understanding the mechanism of 3'-5' nucleotide addition in tRNA(His) maturation. ..
  9. Cheng C, Chen C, Luo Y, Chen W, Chang S, Lyu P, et al. Crystal structure and biophysical characterisation of Helicobacter pylori phosphopantetheine adenylyltransferase. Biochem Biophys Res Commun. 2011;408:356-61 pubmed publisher
    ..However, the interactions between the active-site residues of HpPPAT and CoA are not identical to those of other PPATs. Finally, CoA binding affects HpPPAT thermal denaturation...
  10. Kleczkowski L, Geisler M, Fitzek E, Wilczynska M. A common structural blueprint for plant UDP-sugar-producing pyrophosphorylases. Biochem J. 2011;439:375-9 pubmed publisher
    ..Molecular mobility between these domains plays an important role in substrate binding and catalysis. Evolutionary relationships and the role of (de)oligomerization as a regulatory mechanism are discussed. ..
  11. Talsky K, Collins K. Initiation by a eukaryotic RNA-dependent RNA polymerase requires looping of the template end and is influenced by the template-tailing activity of an associated uridyltransferase. J Biol Chem. 2010;285:27614-23 pubmed publisher
    ..Overall, our findings give new perspective on mechanisms of RDR initiation and demonstrate that non-RDR subunits of an RDRC can affect the specificity of product synthesis. ..
  12. Jackman J, Gott J, Gray M. Doing it in reverse: 3'-to-5' polymerization by the Thg1 superfamily. RNA. 2012;18:886-99 pubmed publisher
    ..We also discuss possible evolutionary origins of Thg1 family-catalyzed 3'-to-5' addition activities and their implications for the currently observed phylogenetic distribution of Thg1-related enzymes in biology. ..
  13. Willer T, Lee H, Lommel M, Yoshida Moriguchi T, de Bernabe D, Venzke D, et al. ISPD loss-of-function mutations disrupt dystroglycan O-mannosylation and cause Walker-Warburg syndrome. Nat Genet. 2012;44:575-80 pubmed publisher
    ..Finally, we show that recessive mutations in ISPD abolish the initial step in laminin-binding glycan synthesis by disrupting dystroglycan O-mannosylation. This establishes a new mechanism for WWS pathophysiology. ..
  14. Minasaki R, Eckmann C. Subcellular specialization of multifaceted 3'end modifying nucleotidyltransferases. Curr Opin Cell Biol. 2012;24:314-22 pubmed publisher
    ..Enzymes responsible for such non-templated additions are non-canonical RNA nucleotidyltransferases, which possess surprising flexibility in RNA substrate selection and enzymatic activity...
  15. Pages V, Santa Maria S, Prakash L, Prakash S. Role of DNA damage-induced replication checkpoint in promoting lesion bypass by translesion synthesis in yeast. Genes Dev. 2009;23:1438-49 pubmed publisher
  16. Asención Diez M, Demonte A, Giacomelli J, Garay S, Rodrigues D, Hofmann B, et al. Functional characterization of GDP-mannose pyrophosphorylase from Leptospira interrogans serovar Copenhageni. Arch Microbiol. 2010;192:103-14 pubmed publisher
    ..Our studies provide insights into the structure of a novel molecular target, which could be useful for detection of leptospirosis and for the development of anti-leptospiral drugs. ..
  17. Hicks J, Chute C, Paulsen M, Ragland R, Howlett N, Gueranger Q, et al. Differential roles for DNA polymerases eta, zeta, and REV1 in lesion bypass of intrastrand versus interstrand DNA cross-links. Mol Cell Biol. 2010;30:1217-30 pubmed publisher
  18. Wyman S, Knouf E, Parkin R, Fritz B, Lin D, Dennis L, et al. Post-transcriptional generation of miRNA variants by multiple nucleotidyl transferases contributes to miRNA transcriptome complexity. Genome Res. 2011;21:1450-61 pubmed publisher
  19. Lee S, Talsky K, Collins K. A single RNA-dependent RNA polymerase assembles with mutually exclusive nucleotidyl transferase subunits to direct different pathways of small RNA biogenesis. RNA. 2009;15:1363-74 pubmed publisher
    ..The biochemical and biological phenotypes of RDRC subunit disruption reveal a previously unanticipated complexity of Rdr-dependent sRNA biogenesis in vivo. ..
  20. Hashimoto K, Cho Y, Yang I, Akagi J, Ohashi E, Tateishi S, et al. The vital role of polymerase ? and REV1 in mutagenic, but not correct, DNA synthesis across benzo[a]pyrene-dG and recruitment of polymerase ? by REV1 to replication-stalled site. J Biol Chem. 2012;287:9613-22 pubmed publisher
    ..This indicates that a non-Y family polymerase(s) can insert a nucleotide opposite BPDE-dG, but the subsequent extension from miscoding termini depends on REV1-pol? in a RAD18-dependent manner. ..
  21. Kikuchi S, Hara K, Shimizu T, Sato M, Hashimoto H. Structural basis of recruitment of DNA polymerase ? by interaction between REV1 and REV7 proteins. J Biol Chem. 2012;287:33847-52 pubmed
    ..Our structure reveals the basis of DNA polymerase ? (a complex of REV3 and REV7) recruitment to the stalled replication fork and provides insight into the mechanism of polymerase switching. ..
  22. Heinemann I, Nakamura A, O Donoghue P, Eiler D, Soll D. tRNAHis-guanylyltransferase establishes tRNAHis identity. Nucleic Acids Res. 2012;40:333-44 pubmed publisher
    ..The crystal structure of human Thg1 revealed a fascinating structural similarity to 5'???3' polymerases, indicating that Thg1 derives from classical polymerases and evolved to assume its specific function in tRNA(His) processing. ..
  23. Li X, Wu J, Gao D, Wang H, Sun L, Chen Z. Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects. Science. 2013;341:1390-4 pubmed publisher
    ..cGas(-/-) mice were more susceptible to lethal infection with herpes simplex virus 1 (HSV1) than wild-type mice. We also show that cGAMP is an adjuvant that boosts antigen-specific T cell activation and antibody production in mice. ..
  24. Abad M, Long Y, Willcox A, Gott J, Gray M, Jackman J. A role for tRNA(His) guanylyltransferase (Thg1)-like proteins from Dictyostelium discoideum in mitochondrial 5'-tRNA editing. RNA. 2011;17:613-23 pubmed publisher
    ..discoideum suggests that gene duplication and divergence during evolution has resulted in paralogous proteins that use 3'-5' nucleotide addition reactions for diverse biological functions in the same organism. ..
  25. Bar Peled M, O Neill M. Plant nucleotide sugar formation, interconversion, and salvage by sugar recycling. Annu Rev Plant Biol. 2011;62:127-55 pubmed publisher
    ..Nevertheless, our understanding of these pathways at the single cell level is far from complete. ..
  26. Arakane Y, Baguinon M, Jasrapuria S, Chaudhari S, Doyungan A, Kramer K, et al. Both UDP N-acetylglucosamine pyrophosphorylases of Tribolium castaneum are critical for molting, survival and fecundity. Insect Biochem Mol Biol. 2011;41:42-50 pubmed publisher
    ..However, both of these genes appear to have additional critical role(s) unrelated to chitin synthesis, presumably in the glycosylation of proteins and/or secondary metabolites...
  27. Yang T, Bar Peled M. Identification of a novel UDP-sugar pyrophosphorylase with a broad substrate specificity in Trypanosoma cruzi. Biochem J. 2010;429:533-43 pubmed publisher
  28. Heinemann I, O Donoghue P, Madinger C, Benner J, Randau L, Noren C, et al. The appearance of pyrrolysine in tRNAHis guanylyltransferase by neutral evolution. Proc Natl Acad Sci U S A. 2009;106:21103-8 pubmed publisher
    ..This indicates that even the most unusual amino acid can play an ordinary role in proteins. ..
  29. Lackovic K, Parisot J, Sleebs N, Baell J, Debien L, Watson K, et al. Inhibitors of Leishmania GDP-mannose pyrophosphorylase identified by high-throughput screening of small-molecule chemical library. Antimicrob Agents Chemother. 2010;54:1712-9 pubmed publisher
    ..We have identified novel candidate compounds for the design and synthesis of antileishmanial therapeutics. ..
  30. Boniecki M, Rho S, Tukalo M, Hsu J, Romero E, Martinis S. Leucyl-tRNA synthetase-dependent and -independent activation of a group I intron. J Biol Chem. 2009;284:26243-50 pubmed publisher
    ..The activity of the minimized bI4 intron was enhanced in vitro by the presence of the bI4 maturase or LeuRS. ..
  31. Rao B, Maris E, Jackman J. tRNA 5'-end repair activities of tRNAHis guanylyltransferase (Thg1)-like proteins from Bacteria and Archaea. Nucleic Acids Res. 2011;39:1833-42 pubmed publisher
    ..These data support more widespread roles for 3'-5' nucleotide addition reactions in biology than previously expected. ..
  32. Burroughs A, Ando Y, de Hoon M, Tomaru Y, Nishibu T, Ukekawa R, et al. A comprehensive survey of 3' animal miRNA modification events and a possible role for 3' adenylation in modulating miRNA targeting effectiveness. Genome Res. 2010;20:1398-410 pubmed publisher
  33. Issur M, Geiss B, Bougie I, Picard Jean F, Despins S, Mayette J, et al. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009;15:2340-50 pubmed publisher
    ..Our study provides biochemical evidence that flaviviruses encode a complete RNA capping machinery. ..
  34. Sun L, Wu J, Du F, Chen X, Chen Z. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science. 2013;339:786-91 pubmed publisher
    ..cGAS bound to DNA in the cytoplasm and catalyzed cGAMP synthesis. These results indicate that cGAS is a cytosolic DNA sensor that induces interferons by producing the second messenger cGAMP...
  35. Chowdhury M, Dosche C, Löhmannsröben H, Leimkuhler S. Dual role of the molybdenum cofactor biosynthesis protein MOCS3 in tRNA thiolation and molybdenum cofactor biosynthesis in humans. J Biol Chem. 2012;287:17297-307 pubmed publisher
    ..The cellular localization results showed that extension of the C terminus with an additional glycine of MOCS2A and URM1 altered the localization of MOCS3 from the cytosol to the nucleus. ..
  36. Preston M, Phizicky E. The requirement for the highly conserved G-1 residue of Saccharomyces cerevisiae tRNAHis can be circumvented by overexpression of tRNAHis and its synthetase. RNA. 2010;16:1068-77 pubmed publisher
  37. Yates L, Fleurdépine S, Rissland O, De Colibus L, Harlos K, Norbury C, et al. Structural basis for the activity of a cytoplasmic RNA terminal uridylyl transferase. Nat Struct Mol Biol. 2012;19:782-787 pubmed publisher
    ..Overall, our structures provide a basis for understanding the activity of Cid1 and a mechanism of UTP selectivity conserved in its human orthologs, suggesting potential implications for anticancer drug design. ..
  38. Swan M, Johnson R, Prakash L, Prakash S, Aggarwal A. Structure of the human Rev1-DNA-dNTP ternary complex. J Mol Biol. 2009;390:699-709 pubmed publisher
  39. Zhang X, Shi H, Wu J, Zhang X, Sun L, Chen C, et al. Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING. Mol Cell. 2013;51:226-35 pubmed publisher
    ..The crystal structure of STING bound to 2'3'-cGAMP revealed the structural basis of this high-affinity binding and a ligand-induced conformational change in STING that may underlie its activation. ..
  40. Lunde B, Magler I, Meinhart A. Crystal structures of the Cid1 poly (U) polymerase reveal the mechanism for UTP selectivity. Nucleic Acids Res. 2012;40:9815-24 pubmed publisher
    ..By mutating this histidine to an asparagine residue in Cid1, we diminished Cid1's activity for UTP addition and improved ATP incorporation, supporting that this residue is important for UTP selectivity. ..
  41. Munoz Tello P, Gabus C, Thore S. Functional implications from the Cid1 poly(U) polymerase crystal structure. Structure. 2012;20:977-86 pubmed publisher
    ..Our study underlines the Cid1 RNA binding properties, a feature with critical implications for miRNAs, histone mRNAs, and, more generally, cellular RNA degradation. ..
  42. Zhou Y, Wang J, Zhang Y, Wang Z. The catalytic function of the Rev1 dCMP transferase is required in a lesion-specific manner for translesion synthesis and base damage-induced mutagenesis. Nucleic Acids Res. 2010;38:5036-46 pubmed publisher
    ..These results show that the catalytic function of the Rev1 dCMP transferase is required in a lesion-specific manner for translesion synthesis and base damage-induced mutagenesis. ..
  43. Kim N, Mudrak S, Jinks Robertson S. The dCMP transferase activity of yeast Rev1 is biologically relevant during the bypass of endogenously generated AP sites. DNA Repair (Amst). 2011;10:1262-71 pubmed publisher
    ..These results demonstrate that the catalytic activity of Rev1 is biologically relevant and is required specifically for dCMP insertion during the bypass of endogenous AP sites. ..
  44. Hara K, Hashimoto H, Murakumo Y, Kobayashi S, Kogame T, Unzai S, et al. Crystal structure of human REV7 in complex with a human REV3 fragment and structural implication of the interaction between DNA polymerase zeta and REV1. J Biol Chem. 2010;285:12299-307 pubmed publisher
    ..Our results will provide a general structural basis for understanding the REV7 interaction. ..
  45. Ren G, Chen X, Yu B. Uridylation of miRNAs by hen1 suppressor1 in Arabidopsis. Curr Biol. 2012;22:695-700 pubmed publisher
    ..This study shall have implications on piRNA uridylation in hen1 in animals. ..
  46. Brown J, Fowler J, Suo Z. Kinetic basis of nucleotide selection employed by a protein template-dependent DNA polymerase. Biochemistry. 2010;49:5504-10 pubmed publisher
  47. Ablasser A, Goldeck M, Cavlar T, Deimling T, Witte G, Röhl I, et al. cGAS produces a 2'-5'-linked cyclic dinucleotide second messenger that activates STING. Nature. 2013;498:380-4 pubmed publisher
    ..This 13-membered ring structure defines a novel class of second messenger molecules, extending the family of 2'-5'-linked antiviral biomolecules. ..
  48. Wubben T, Mesecar A. Kinetic, thermodynamic, and structural insight into the mechanism of phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis. J Mol Biol. 2010;404:202-19 pubmed publisher
    ..We suggest that the proposed kinetic mechanism and asymmetric character in MtPPAT ligand binding may provide a means of reaction and pathway regulation in addition to that of the previously determined CoA feedback...
  49. Hyde S, Eckenroth B, Smith B, Eberley W, Heintz N, Jackman J, et al. tRNA(His) guanylyltransferase (THG1), a unique 3'-5' nucleotidyl transferase, shares unexpected structural homology with canonical 5'-3' DNA polymerases. Proc Natl Acad Sci U S A. 2010;107:20305-10 pubmed publisher
    ..The ability of the same structural architecture to catalyze both 5'-3' and 3'-5' reactions raises important questions concerning selection of the 5'-3' mechanism during the evolution of nucleotide polymerases. ..
  50. Kinch L, Yarbrough M, Orth K, Grishin N. Fido, a novel AMPylation domain common to fic, doc, and AvrB. PLoS ONE. 2009;4:e5818 pubmed publisher
    ..These results suggest that fic, doc, and AvrB stem from a common ancestor that has evolved to AMPylate protein substrates. ..
  51. Wiltrout M, Walker G. Proteasomal regulation of the mutagenic translesion DNA polymerase, Saccharomyces cerevisiae Rev1. DNA Repair (Amst). 2011;10:169-75 pubmed publisher
    ..These results support a model that proteasomal degradation acts as a regulatory system of mutagenic TLS mediated by Rev1. ..
  52. Zhao Y, Yu Y, Zhai J, Ramachandran V, Dinh T, Meyers B, et al. The Arabidopsis nucleotidyl transferase HESO1 uridylates unmethylated small RNAs to trigger their degradation. Curr Biol. 2012;22:689-94 pubmed publisher
    ..We show that uridylation leads to miRNA degradation, and the degradation is most likely through an enzyme that is distinct from that causing the 3' truncation in hen1 mutants. ..
  53. Knouf E, Wyman S, Tewari M. The human TUT1 nucleotidyl transferase as a global regulator of microRNA abundance. PLoS ONE. 2013;8:e69630 pubmed publisher
    ..In conclusion, our results suggest that TUT1 affects miRNAs through both a direct effect on 3' nucleotide additions to specific miRNAs and a separate, indirect effect on miRNA abundance more globally. ..