ribonuclease h

Summary

Summary: A ribonuclease that specifically cleaves the RNA moiety of RNA:DNA hybrids. It has been isolated from a wide variety of prokaryotic and eukaryotic organisms as well as RETROVIRUSES.

Top Publications

  1. Kouzminova E, Kadyrov F, Kuzminov A. RNase HII Saves rnhA Mutant Escherichia coli from R-Loop-Associated Chromosomal Fragmentation. J Mol Biol. 2017;429:2873-2894 pubmed publisher
  2. DeStefano J, Buiser R, Mallaber L, Bambara R, Fay P. Human immunodeficiency virus reverse transcriptase displays a partially processive 3' to 5' endonuclease activity. J Biol Chem. 1991;266:24295-301 pubmed
    We have examined the ribonuclease H (RNase H) activity of human immunodeficiency virus reverse transcriptase (HIV-RT) using a natural sequence 83-nucleotide-long RNA template to which was hybridized a DNA oligomer...
  3. Mutisya D, Hardcastle T, Cheruiyot S, Pallan P, Kennedy S, Egli M, et al. Amide linkages mimic phosphates in RNA interactions with proteins and are well tolerated in the guide strand of short interfering RNAs. Nucleic Acids Res. 2017;45:8142-8155 pubmed publisher
    ..Our results suggest that an amide can mimic important hydrogen bonding interactions with proteins required for RNAi activity and may be a promising modification for optimization of biological properties of siRNAs. ..
  4. Iwamoto N, Butler D, Svrzikapa N, Mohapatra S, Zlatev I, Sah D, et al. Control of phosphorothioate stereochemistry substantially increases the efficacy of antisense oligonucleotides. Nat Biotechnol. 2017;35:845-851 pubmed publisher
    ..Further, we elucidated a triplet stereochemical code in the stereopure ASOs, 3'-SpSpRp, that promotes target RNA cleavage by RNase H1 in vitro and provides a more durable response in mice than stereorandom ASOs. ..
  5. Tan S, Chadha S, Liu Y, Gabasova E, Perera D, Ahmed K, et al. A Class of Environmental and Endogenous Toxins Induces BRCA2 Haploinsufficiency and Genome Instability. Cell. 2017;169:1105-1118.e15 pubmed publisher
    ..These findings suggest a model wherein carcinogenesis in BRCA2 mutation carriers can be incited by compounds found pervasively in the environment and generated endogenously in certain tissues with implications for public health. ..
  6. Heider M, Burkhart B, Santangelo T, Gardner A. Defining the RNaseH2 enzyme-initiated ribonucleotide excision repair pathway in Archaea. J Biol Chem. 2017;292:8835-8845 pubmed publisher
    ..The lack of redundancies in ribonucleotide repair in archaea perhaps suggests a more ancestral form of ribonucleotide excision repair compared with the eukaryotic pathway. ..
  7. Döring J, Hurek T. Arm-specific cleavage and mutation during reverse transcription of 2?,5?-branched RNA by Moloney murine leukemia virus reverse transcriptase. Nucleic Acids Res. 2017;45:3967-3984 pubmed publisher
    ..Our observed interplay between M-MLV RT and bRNA would be compatible with a bRNA-mediated control of retroviral and related retrotransposon replication. ..
  8. Pathak V, Temin H. Broad spectrum of in vivo forward mutations, hypermutations, and mutational hotspots in a retroviral shuttle vector after a single replication cycle: deletions and deletions with insertions. Proc Natl Acad Sci U S A. 1990;87:6024-8 pubmed
    ..The analysis also indicates that fragments of viral RNA generated by the viral RNase H endonuclease are used as templates and contribute to the sequences inserted at the deletion junctions. ..
  9. Powell M, Beard W, Bebenek K, Howard K, Le Grice S, Darden T, et al. Residues in the alphaH and alphaI helices of the HIV-1 reverse transcriptase thumb subdomain required for the specificity of RNase H-catalyzed removal of the polypurine tract primer. J Biol Chem. 1999;274:19885-93 pubmed
    ..Our results indicate that residues in the thumb subdomain and the minor groove binding track in particular, are crucial for unique interactions between RT and the PPT required for correct positioning and precise RNase H cleavage. ..

More Information

Publications25

  1. Günther C, Kind B, Reijns M, Berndt N, Martínez Bueno M, Wolf C, et al. Defective removal of ribonucleotides from DNA promotes systemic autoimmunity. J Clin Invest. 2015;125:413-24 pubmed publisher
    ..Collectively, our findings implicate RNase H2 in the pathogenesis of SLE and suggest a role of DNA damage-associated pathways in the initiation of autoimmunity. ..
  2. Gunderson S, Polycarpou Schwarz M, Mattaj I. U1 snRNP inhibits pre-mRNA polyadenylation through a direct interaction between U1 70K and poly(A) polymerase. Mol Cell. 1998;1:255-64 pubmed
    ..Conservation of the U1 70K inhibitory domains suggests that polyadenylation regulation via PAP inhibition may be more widespread than previously thought. ..
  3. Nanavaty V, Sandhu R, Jehi S, Pandya U, Li B. Trypanosoma brucei RAP1 maintains telomere and subtelomere integrity by suppressing TERRA and telomeric RNA:DNA hybrids. Nucleic Acids Res. 2017;45:5785-5796 pubmed publisher
  4. Liang X, Sun H, Shen W, Wang S, Yao J, Migawa M, et al. Antisense oligonucleotides targeting translation inhibitory elements in 5' UTRs can selectively increase protein levels. Nucleic Acids Res. 2017;45:9528-9546 pubmed publisher
    ..Importantly, ASOs targeting ACP1 mRNA significantly increased the level of ACP1 protein in mice, suggesting that this approach has therapeutic and research potentials. ..
  5. Pei Y, Wang C, Yan S, Liu G. Past, Current, and Future Developments of Therapeutic Agents for Treatment of Chronic Hepatitis B Virus Infection. J Med Chem. 2017;60:6461-6479 pubmed publisher
    ..including entry inhibitors, transcription inhibitors, nucleoside/nucleotide analogues, inhibitors of viral ribonuclease H (RNase H), modulators of viral capsid assembly, inhibitors of HBV surface antigen (HBsAg) secretion, RNA ..
  6. Shen W, Sun H, De Hoyos C, Bailey J, Liang X, Crooke S. Dynamic nucleoplasmic and nucleolar localization of mammalian RNase H1 in response to RNAP I transcriptional R-loops. Nucleic Acids Res. 2017;45:10672-10692 pubmed publisher
    ..We conclude that Top1 and RNase H1 are partially functionally redundant in mammalian cells to suppress RNAP I transcription-associate R-loops. ..
  7. Lee N, Le Sage V, Nanni A, Snyder D, Cooper V, Lakdawala S. Genome-wide analysis of influenza viral RNA and nucleoprotein association. Nucleic Acids Res. 2017;45:8968-8977 pubmed publisher
    ..Taken together, our genome-wide study of NP-vRNA interaction has implications for the understanding of influenza vRNA architecture and genome packaging. ..
  8. Schatz O, Cromme F, Gruninger Leitch F, Le Grice S. Point mutations in conserved amino acid residues within the C-terminal domain of HIV-1 reverse transcriptase specifically repress RNase H function. FEBS Lett. 1989;257:311-4 pubmed
    ..These mutant proteins were expressed in Escherichia coli and purified by Ni2+-nitrilotriacetic acid affinity chromatography. Both enzymes are clearly defective in RNase H function, but exhibit wild type reverse transcriptase activity. ..
  9. Parajuli S, Teasley D, Murali B, Jackson J, Vindigni A, Stewart S. Human ribonuclease H1 resolves R-loops and thereby enables progression of the DNA replication fork. J Biol Chem. 2017;292:15216-15224 pubmed publisher
  10. La Teana A, Gualerzi C, Brimacombe R. From stand-by to decoding site. Adjustment of the mRNA on the 30S ribosomal subunit under the influence of the initiation factors. RNA. 1995;1:772-82 pubmed
  11. Althaus I, Chou J, Gonzales A, Deibel M, Chou K, Kezdy F, et al. Kinetic studies with the non-nucleoside HIV-1 reverse transcriptase inhibitor U-88204E. Biochemistry. 1993;32:6548-54 pubmed
    ..The inhibitor did not inhibit the RNase H function of HIV-1 RT nor did it impair the RNA-directed DNA polymerase activity of HIV-2 RT. These data thus demonstrate the unique specificity of U-88204E for HIV-1 RT. ..
  12. Palaniappan C, Wisniewski M, Jacques P, Le Grice S, Fay P, Bambara R. Mutations within the primer grip region of HIV-1 reverse transcriptase result in loss of RNase H function. J Biol Chem. 1997;272:11157-64 pubmed
    ..Since mutants P226A and F227A carried out these latter reactions normally, these two residues specifically influence 5'-RNA-directed RNase H catalysis. ..
  13. Hagedorn P, Hansen B, Koch T, Lindow M. Managing the sequence-specificity of antisense oligonucleotides in drug discovery. Nucleic Acids Res. 2017;45:2262-2282 pubmed publisher
    ..Since potential adverse effects related to unintended targeting are sequence-dependent and therefore species-specific, in vitro toxicology assays in human cells are especially relevant in oligonucleotide drug discovery. ..
  14. Credle J, Itoh C, Yuan T, Sharma R, Scott E, Workman R, et al. Multiplexed analysis of fixed tissue RNA using Ligation in situ Hybridization. Nucleic Acids Res. 2017;45:e128 pubmed publisher
    ..LISH analysis of FFPE RNA is a novel methodology with broad applications that range from multiplexed gene expression analysis to the sensitive detection of infectious organisms. ..
  15. Schatz O, Mous J, Le Grice S. HIV-1 RT-associated ribonuclease H displays both endonuclease and 3'----5' exonuclease activity. EMBO J. 1990;9:1171-6 pubmed
    We have analysed the mechanism of ribonuclease H (RNaseH) induced cleavage of a defined RNA-DNA hybrid by human immuno-deficiency virus (HIV-1) reverse transcriptase (RT)...
  16. Tang J, Vernekar S, Chen Y, Miller L, Huber A, Myshakina N, et al. Synthesis, biological evaluation and molecular modeling of 2-Hydroxyisoquinoline-1,3-dione analogues as inhibitors of HIV reverse transcriptase associated ribonuclease H and polymerase. Eur J Med Chem. 2017;133:85-96 pubmed publisher
    Human immunodeficiency virus (HIV) reverse transcriptase (RT) associated ribonuclease H (RNase H) remains the only virally encoded enzymatic function not clinically validated as an antiviral target...