Ribonucleases H.

from Wikipedia, the free encyclopedia
Structure comparison of the RNases H. Red spheres are the amino acids of the active center
E. coli ribonuclease HI
Human RNase H2 with subunits A (light blue), B (dark red) and C (pink), purple spheres as the amino acids of the active center and mutation sites (yellow)
Proposed Mechanism of Reaction for HIV RNase H

Ribonuclease H (from Ribonuclease Hybrid , synonymous RNase H ) is a group of enzymes ( ribonucleases ) that break down RNA in DNA - RNA hybrids.

properties

They are divided into two groups, RNase HI (in bacteria ) or RNase H1 (in eukaryotes ) and RNase HII (in bacteria) or RNase H2 (in eukaryotes). While the RNase HI from Escherichia coli (155 aa , 17,600 Da ) and the RNase H1 from humans (286 aa, 32,200 Da, and without mitochondrial signal sequence 260 aa, 29,400 Da) are each monomers , the RNase HII from E. coli ( 198 aa, 21,500 Da) monomeric and the RNase H2 of humans heterotrimeric (RNase H2A with 299 aa and 33,400 Da; RNase H2B with 308 aa and 34,800 Da; RNase H2C with 164 aa and 17,800 Da). An RNase HIII is still formed in a few prokaryotes . RNase H is also encoded by HIV as a protein domain of reverse transcriptase , which is similar to human RNase H1 in terms of protein structure and reaction mechanism and which is necessary for replication .

Mutations in the human RNase H2 can lead to Aicardi-Goutières syndrome .

function

Type H ribonucleases occur in almost all living things and are sequence-unspecific endonucleases that hydrolyse the phosphoric acid ester bond of RNA in double strands of DNA and RNA , creating a 3'- hydroxyl group and a 5'- phosphate group . The RNase H1 is involved in the replication of mitochondrial DNA . RNase H1 and H2 are involved in breaking down the R-loop . In prokaryotes and lower eukaryotes, RNases H are not essential, in higher eukaryotes they are essential. RNase H1 and H2 have different substrate preferences , but overlapping functions in the mitochondrion.

RNase H1

RNase H1 requires at least four ribonucleotides as a substrate and is inhibited by deoxyribonucleotides in the same strand. Therefore, RNase H1 is unlikely to be involved in the degradation of the RNA primers on the Okazaki fragments during DNA replication . A gene knockout of RNase HI in E. coli produces a temperature-sensitive phenotype , but is not lethal. In Saccharomyces cerevisiae , a gene knockout of RNase H1 disrupts the response to cell stress and is also not lethal. In many eukaryotes, including mammals, RNase H1 has a mitochondrial signal sequence, as a result of which it occurs in the cell outside the mitochondrion with the signal sequence and inside the mitochondrion without the signal sequence. A gene knockout of RNase H1 in mice is lethal during embryogenesis due to impaired replication of the mitochondrial DNA, presumably due to the impaired breakdown of the R-loop.

RNase H2

The RNase H2 subunit A is homologous to the RNase HII, while the subunits B and C have no prokaryotic homolog and vary comparatively strongly within the eukaryotes. The subunit B mediates protein-protein interactions between RNase H2 and PCNA , whereby RNase H2 is localized to the site of DNA replication. Prokaryotic RNase HII have a lower reaction rate compared to RNase H2 and are inhibited by deoxyribonucleotides at the 5 'end. RNase 2 is also involved in DNA repair ( nucleotide excision repair ) by removing incorrectly incorporated ribonucleotides from DNA. In the mammalian nucleus, RNase H2 is the more active RNase H.

RNase HIII

In a few prokaryotes , an RNase III is still formed, which is structurally similar to RNase II, but resembles RNase I in terms of the reaction mechanism. While RNase III occurs rather sporadically in prokaryotes, it is found somewhat more frequently in archaea and mostly instead of RNase HI.

Individual evidence

  1. ↑ E. coli PDB  2RN2 , T. maritima PDB  303F , B. stearothermophilus PDB  2D0B , H. sapiens H1 PDB  2QK9 , H. sapiens PDB  3P56 .
  2. ↑ M. Figiel, H. Chon, SM Cerritelli, M. Cybulska, RJ Crouch, M. Nowotny: The structural and biochemical characterization of human RNase H2 complex reveals the molecular basis for substrate recognition and Aicardi-Goutières syndrome defects. In: Journal of Biological Chemistry . Volume 286, Number 12, March 2011, pp. 10540-10550, doi : 10.1074 / jbc.M110.181974 , PMID 21177858 , PMC 3060507 (free full text).
  3. ↑ a b c d e f g h i S. M. Cerritelli, RJ Crouch: Ribonuclease H: the enzymes in eukaryotes. In: The FEBS journal. Volume 276, number 6, March 2009, pp. 1494-1505, doi : 10.1111 / j.1742-4658.2009.06908.x , PMID 19228196 , PMC 2746905 (free full text).
  4. ↑ a b M. Figiel, M. Nowotny: Crystal structure of RNase H3-substrate complex reveals parallel evolution of RNA / DNA hybrid recognition. In: Nucleic acids research. Volume 42, number 14, August 2014, pp. 9285-9294, doi : 10.1093 / nar / gku615 , PMID 25016521 , PMC 4132731 (free full text).
  5. ↑ JF Davies, Z. Hostomska, Z. Hostomsky, SR Jordan, DA Matthews: Crystal structure of the ribonuclease H domain of HIV-1 reverse transcriptase. In: Science . Volume 252, Number 5002, April 1991, pp. 88-95, doi : 10.1126 / science.1707186 , PMID 1707186 .
  6. ↑ J. Hansen, T. Schulze, W. Mellert, K. Moelling : Identification and characterization of HIV-specific RNase H by monoclonal antibody. In: The EMBO Journal . Volume 7, Number 1, January 1988, pp. 239-243, PMID 2452083 , PMC 454263 (free full text).
  7. ↑ YJ Crow, A. Leitch, BE Hayward, A. Garner, R. Parmar, E. Griffith, M. Ali, C. Semple, J. Aicardi, R. Babul-Hirji, C. Baumann, P. Baxter, E . Bertini, KE Chandler, D. Chitayat, D. Cau, C. Déry, E. Fazzi, C. Goizet, MD King, J. Klepper, D. Lacombe, G. Lanzi, H. Lyall, ML Martínez-Frías, M. Mathieu, C. McKeown, A. Monier, Y. Oade, OW Quarrell, CD Rittey, RC Rogers, A. Sanchis, JB Stephenson, U. Tacke, M. Till, JL Tolmie, P. Tomlin, T. Voit , B. Weschke, CG Woods, P. Lebon, DT Bonthron, CP Ponting, AP Jackson: Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutières syndrome and mimic congenital viral brain infection. In: Nature genetics. Volume 38, Number 8, August 2006, pp. 910-916, doi : 10.1038 / ng1842 , PMID 16845400 .
  8. ↑ a b c T. Tadokoro, S. Kanaya: Ribonuclease H: molecular diversities, substrate binding domains, and catalytic mechanism of the prokaryotic enzymes. In: The FEBS journal. Volume 276, Number 6, March 2009, pp. 1482-1493, doi : 10.1111 / j.1742-4658.2009.06907.x , PMID 19228197 .
  9. ↑ Amon JD, Koshland D: RNase H enables efficient repair of R-loop induced DNA damage . In: eLife . 5, December 2016, p. E20533. doi : 10.7554 / eLife.20533 . PMID 27938663 . PMC 5215079 (free full text).
  10. ↑ a b Lima WF, Murray HM, Damle SS, Hart CE, Hung G, De Hoyos CL, Liang XH, Crooke ST: Viable RNaseH1 knockout mice show RNaseH1 is essential for R loop processing, mitochondrial and liver function . In: Nucleic Acids Research . 44, No. 11, June 2016, pp. 5299-312. doi : 10.1093 / nar / gkw350 . PMID 27131367 . PMC 4914116 (free full text).
  11. ↑ Arudchandran A, Cerritelli S, Narimatsu S, Itaya M, Shin DY, Shimada Y, Crouch RJ: The absence of ribonuclease H1 or H2 alters the sensitivity of Saccharomyces cerevisiae to hydroxyurea, caffeine and ethyl methanesulphonate: implications for roles of RNases H in DNA replication and repair . In: Genes to Cells . 5, No. 10, 2000, pp. 789-802. doi : 10.1046 / j.1365-2443.2000.00373.x . PMID 11029655 .
  12. ↑ Cerritelli SM, Frolova EG, Feng C, Grinberg A, Love PE, Crouch RJ: Failure to produce mitochondrial DNA results in embryonic lethality in Rnaseh1 null mice . In: Molecular Cell . 11, No. 3, 2003, pp. 807-15. doi : 10.1016 / s1097-2765 (03) 00088-1 . PMID 12667461 .
  13. ↑ Reyes A, Melchionda L, Nasca A, Carrara F, Lamantea E, Zanolini A, Lamperti C, Fang M, Zhang J, Ronchi D, Bonato S, Fagiolari G, Moggio M, Ghezzi D, Zeviani M: RNASEH1 Mutations Impair mtDNA Replication and Cause Adult-Onset Mitochondrial Encephalomyopathy . In: American Journal of Human Genetics . 97, No. 1, July 2015, pp. 186–93. doi : 10.1016 / j.ajhg.2015.05.013 . PMID 26094573 . PMC 4572567 (free full text).
  14. ↑ Thomas Hollis, Nadine M. Shaban: Allen W. Nicholson (Ed.): Ribonucleases  (= Nucleic Acids and Molecular Biology). Springer Berlin Heidelberg, January 1, 2011, ISBN 9783642210778 , pp. 299-317, doi : 10.1007 / 978-3-642-21078-5_12 .
  15. ↑ Chon H, Vassilev A, DePamphilis ML, Zhao Y, Zhang J, Burgers PM, Crouch RJ, Cerritelli SM: Contributions of the two accessory subunits, RNASEH2B and RNASEH2C, to the activity and properties of the human RNase H2 complex . In: Nucleic Acids Research . 37, No. 1, January 2009, pp. 96-110. doi : 10.1093 / nar / gkn913 . PMID 19015152 . PMC 2615623 (free full text).
  16. ↑ a b c Reijns MA, Jackson AP: ribonuclease H2 disease in health and . In: Biochemical Society Transactions . 42, No. 4, August 2014, pp. 717-25. doi : 10.1042 / BST20140079 . PMID 25109948 .
  17. ↑ Chon H, Vassilev A, DePamphilis ML, Zhao Y, Zhang J, Burgers PM, Crouch RJ, Cerritelli SM: Contributions of the two accessory subunits, RNASEH2B and RNASEH2C, to the activity and properties of the human RNase H2 complex . In: Nucleic Acids Research . 37, No. 1, January 2009, pp. 96-110. doi : 10.1093 / nar / gkn913 . PMID 19015152 . PMC 2615623 (free full text).
  18. ↑ Wahba L, Amon JD, Koshland D, Vuica-Ross M: RNase H and multiple RNA biogenesis factors cooperate to prevent RNA: DNA hybrids from generating genome instability . In: Molecular Cell . 44, No. 6, December 2011, pp. 978-88. doi : 10.1016 / j.molcel.2011.10.017 . PMID 22195970 . PMC 3271842 (free full text).
  19. ↑ Kim N, Huang SN, Williams JS, Li YC, Clark AB, Cho JE, Kunkel TA, Pommier Y, Jinks-Robertson S: Mutagenic processing of ribonucleotides in DNA by yeast topoisomerase I . In: Science . 332, No. 6037, June 2011, pp. 1561-4. doi : 10.1126 / science.1205016 . PMID 21700875 . PMC 3380281 (free full text).
  20. ↑ Ohtani N, Haruki M, Morikawa M, Crouch RJ, Itaya M, Kanaya S: Identification of the genes encoding Mn2 + -dependent RNase HII and Mg2 + -dependent RNase HIII from Bacillus subtilis: classification of RNases H into three families . In: Biochemistry . 38, No. 2, January 1999, pp. 605-18. doi : 10.1021 / bi982207z . PMID 9888800 .
  21. ↑ Kochiwa H, Tomita M, Kanai A: Evolution of ribonuclease H genes in prokaryotes to avoid inheritance of redundant genes . In: BMC Evolutionary Biology . July 7, 2007, p. 128. doi : 10.1186 / 1471-2148-7-128 . PMID 17663799 . PMC 1950709 (free full text).