Ribonuclease

From Proteopedia

Ribonuclease A (magenta) complex with thymidylic acid DNA tetramer (pink), 1rta

Drag the structure with the mouse to rotate

1 Function
2 Relevance
3 Disease
4 Active Site of Ribonuclease A
5 3D Structures of Ribonuclease

Function

Ribonuclease (RNase) degrades RNA. The endonucleases cleave single or double stranded RNA. Exo-RNases remove terminal nucleotide from the ends of the RNA molecule.

RNase A or RNase I endonuclease which cleaves C or U of single-stranded RNA (ssRNA)^[1]. For details see RNase A, RNase A Oligomers, Ribonuclease A Catalysis, RNaseA Nobel Prizes, User:R. Jeremy Johnson/RNaseA and RNase A NMR.
RNase BA is RNase from Bacillus amyloliquefaciens.
RNase D exonuclease which degrades 3'-end pre-tRNA^[2].
RNase H endonuclease which cleaves RNA/DNA double-strand to produce ssDNA^[3].
RNase II exonuclease which degrades 3'-end ssRNA^[4].
RNase III endonuclease which cleaves double stranded rRNA^[5].
RNase III Dicer cleaves dsRNA to small interfering RNA and microRNA^[6]. See details in Dicer.
RNase 4 is the shortest RNase. It shows a high specificity for uridine^[7].
RNase 5 is known as angiogenin and is a potent stimulator of new blood vessels formation^[8].
RNase 6 is a cationic secreted protein with a role in host defense^[9].
RNase 7 is an innate immune defense antimacrobial protein^[10].
RNase E is an endonuclease which plays a role in all aspects of RNA metabolism^[11].
RNase J has exonuclease activity and plays a role in RNA maturation and decay^[12].
RNase L activates the inflammasome during viral infection^[13].
RNase MC1 from bitter gourd has a preference for cleavage at the 5'-end of uridine^[14].
RNase MRP processes RNA from the mitochondrial displacement loop-containing region^[15].
RNase P is an endonuclease which is a ribozyme^[16]. For details see RNase P, RNase P Nobel Prizes.
RNase PH is an exonuclease involved in the trimming of the 3' terminus of tRNA^[17].
RNase Po1 is a G-specific RNase from Pleurotus ostreatus.
RNase Pop2 is involved in the deadenylation of mRNA^[18].
RNase RH is RNase from Rhizopus niveus^[19].
RNase S is RNase A cleaved by subtilisin. For details see RNaseS RNaseB.
RNase SA is RNase from Streptomyces auerofaciens^[20].
RNase T exonuclease which is involved in RNA maturation^[21].
RNase T1 endonuclease which cleaves 3'-end G from ssRNA^[22].
RNase U2 cleaves 3'-end A from ssRNA^[23].
RNase Z is an endonuclease which processes CCA-less tRNA^[24].
α-sarcin is a cytotoxic RNase which cleaves a phosphodiester bond in a conserved rRNA loop and inactivates the ribosome^[25].
oligoribonuclease exonuclease which is an exoribonuclease which cleaves 3'-end of viral RNA-DNA hybrid^[26].
Polynucleotide phosphorylase exonuclease which is a bifunctional enzyme which has exoribonuclease activity^[27].
Binase is a microbial RNase which cleaves endonucleolyticly ssRNA^[28].
Poly(A)-specific RNase cleaves exonucleolyticly the poly(A) tail^[29].
NanoRNase cleaves RNA fragments of 2-5 nucleotides which are generated by RNA degradation^[30].
MiniRNase RNase with the catalytic domain but lacking the specificity domain^[31].

Relevance

The retroviral RNase H inhibitors are investigated as potential antiretroviral (HIV) agents.
α-sarcin is a new anti tumor agent^[32].
RNase Sa, RNase T1 and binase are studied as potential anticancer therapeutic agents^[33].
RNase 6 and RNase 7 show potent antimicrobial activity^[34].
RNase L plays a role in the antiviral response to West Nile virus^[35].
Human tumor cells proliferation is inhibited by tRNase Po1^[36].

Disease

Mutations in RNase T2 are associated with white matter disease of the human brain^[37] and with ovarian tumorigenesis^[38].

Active Site of Ribonuclease A

Ribonuclease A cleaves RNA strands by catalyzing a transphosphorylation reaction where the 2'-OH of the ribose sugar attacks the neighboring phosphate, releasing the ribose on the the other side of the phosphate. This structure shows ribonuclease A (in blue) bound to short DNA strand composed of four thymidines (in pink). Ribonuclease binds tightly to DNA, but since DNA is missing the 2'-OH, ribonuclease does not cleave it. are shown that are important for catalysis. The 3' carbon on the DNA is shown in red--it is the site where the 2'-OH is connected in RNA. The two histidines perform the proton transfers that are needed in the reaction, and the lysine stabilizes the intermediate that is formed as the 2'-OH attacks the phosphate. Ribonuclease cleaves RNA strands best next to cytidine and uridine nucleotides--the reason for this may be seen in a . Notice that the small pyrimidine base is surrounded by protein atoms. A larger purine base would not fit well in this space.^[39]

3D Structures of Ribonuclease

Ribonuclease 3D structures

References

↑ Cho S, Beintema JJ, Zhang J. The ribonuclease A superfamily of mammals and birds: identifying new members and tracing evolutionary histories. Genomics. 2005 Feb;85(2):208-20. PMID:15676279 doi:http://dx.doi.org/10.1016/j.ygeno.2004.10.008
↑ Cudny H, Zaniewski R, Deutscher MP. Escherichia coli RNase D. Catalytic properties and substrate specificity. J Biol Chem. 1981 Jun 10;256(11):5633-7. PMID:6263886
↑ Moelling K, Broecker F, Kerrigan JE. RNase H: specificity, mechanisms of action, and antiviral target. Methods Mol Biol. 2014;1087:71-84. doi: 10.1007/978-1-62703-670-2_7. PMID:24158815 doi:http://dx.doi.org/10.1007/978-1-62703-670-2_7
↑ Lu F, Taghbalout A. The Escherichia coli major exoribonuclease RNase II is a component of the RNA degradosome. Biosci Rep. 2014 Dec 23;34(6):e00166. doi: 10.1042/BSR20140113. PMID:25299745 doi:http://dx.doi.org/10.1042/BSR20140113
↑ PMID:24124o76
↑ Ji X. The mechanism of RNase III action: how dicer dices. Curr Top Microbiol Immunol. 2008;320:99-116. PMID:18268841
↑ Terzyan SS, Peracaula R, de Llorens R, Tsushima Y, Yamada H, Seno M, Gomis-Ruth FX, Coll M. The three-dimensional structure of human RNase 4, unliganded and complexed with d(Up), reveals the basis for its uridine selectivity. J Mol Biol. 1999 Jan 8;285(1):205-14. PMID:9878400 doi:10.1006/jmbi.1998.2288
↑ Kim KW, Park SH, Oh DH, Lee SH, Lim KS, Joo K, Chun YS, Chang SI, Min KM, Kim JC. Ribonuclease 5 coordinates signals for the regulation of intraocular pressure and inhibits neural apoptosis as a novel multi-functional anti-glaucomatous strategy. Biochim Biophys Acta. 2016 Feb;1862(2):145-54. doi: 10.1016/j.bbadis.2015.11.005., Epub 2015 Nov 12. PMID:26581172 doi:http://dx.doi.org/10.1016/j.bbadis.2015.11.005
↑ Prats-Ejarque G, Arranz-Trullen J, Blanco JA, Pulido D, Nogues MV, Moussaoui M, Boix E. The first crystal structure of human RNase6 reveals a novel substrate binding and cleavage site arrangement. Biochem J. 2016 Mar 24. pii: BCJ20160245. PMID:27013146 doi:http://dx.doi.org/10.1042/BCJ20160245
↑ Harder J, Schroder JM. RNase 7, a novel innate immune defense antimicrobial protein of healthy human skin. J Biol Chem. 2002 Nov 29;277(48):46779-84. Epub 2002 Sep 18. PMID:12244054 doi:http://dx.doi.org/10.1074/jbc.M207587200
↑ Mackie GA. RNase E: at the interface of bacterial RNA processing and decay. Nat Rev Microbiol. 2013 Jan;11(1):45-57. doi: 10.1038/nrmicro2930. PMID:23241849 doi:http://dx.doi.org/10.1038/nrmicro2930
↑ Condon C. What is the role of RNase J in mRNA turnover? RNA Biol. 2010 May-Jun;7(3):316-21. Epub 2010 May 26. PMID:20458164
↑ Chakrabarti A, Banerjee S, Franchi L, Loo YM, Gale M Jr, Nunez G, Silverman RH. RNase L activates the NLRP3 inflammasome during viral infections. Cell Host Microbe. 2015 Apr 8;17(4):466-77. doi: 10.1016/j.chom.2015.02.010. Epub, 2015 Mar 26. PMID:25816776 doi:http://dx.doi.org/10.1016/j.chom.2015.02.010
↑ Suzuki A, Yao M, Tanaka I, Numata T, Kikukawa S, Yamasaki N, Kimura M. Crystal structures of the ribonuclease MC1 from bitter gourd seeds, complexed with 2'-UMP or 3'-UMP, reveal structural basis for uridine specificity. Biochem Biophys Res Commun. 2000 Aug 28;275(2):572-6. PMID:10964705 doi:10.1006/bbrc.2000.3318
↑ Potuschak T, Rossmanith W, Karwan R. RNase MRP and RNase P share a common substrate. Nucleic Acids Res. 1993 Jul 11;21(14):3239-43. doi: 10.1093/nar/21.14.3239. PMID:7688115 doi:http://dx.doi.org/10.1093/nar/21.14.3239
↑ Mann H, Ben-Asouli Y, Schein A, Moussa S, Jarrous N. Eukaryotic RNase P: role of RNA and protein subunits of a primordial catalytic ribonucleoprotein in RNA-based catalysis. Mol Cell. 2003 Oct;12(4):925-35. PMID:14580343
↑ Deutscher MP, Marshall GT, Cudny H. RNase PH: an Escherichia coli phosphate-dependent nuclease distinct from polynucleotide phosphorylase. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4710-4. PMID:2455297
↑ Daugeron MC, Mauxion F, Seraphin B. The yeast POP2 gene encodes a nuclease involved in mRNA deadenylation. Nucleic Acids Res. 2001 Jun 15;29(12):2448-55. PMID:11410650
↑ Kurihara H, Mitsui Y, Ohgi K, Irie M, Mizuno H, Nakamura KT. Crystal and molecular structure of RNase Rh, a new class of microbial ribonuclease from Rhizopus niveus. FEBS Lett. 1992 Jul 20;306(2-3):189-92. PMID:1633875
↑ Shaw KL, Grimsley GR, Yakovlev GI, Makarov AA, Pace CN. The effect of net charge on the solubility, activity, and stability of ribonuclease Sa. Protein Sci. 2001 Jun;10(6):1206-15. PMID:11369859 doi:http://dx.doi.org/10.1110/ps.440101
↑ Hsiao YY, Fang WH, Lee CC, Chen YP, Yuan HS. Structural insights into DNA repair by RNase T--an exonuclease processing 3' end of structured DNA in repair pathways. PLoS Biol. 2014 Mar 4;12(3):e1001803. doi: 10.1371/journal.pbio.1001803., eCollection 2014 Mar. PMID:24594808 doi:http://dx.doi.org/10.1371/journal.pbio.1001803
↑ Loverix S, Winqvist A, Stromberg R, Steyaert J. Mechanism of RNase T1: concerted triester-like phosphoryl transfer via a catalytic three-centered hydrogen bond. Chem Biol. 2000 Aug;7(8):651-8. PMID:11048955
↑ Noguchi S. Isomerization mechanism of aspartate to isoaspartate implied by structures of Ustilago sphaerogena ribonuclease U2 complexed with adenosine 3'-monophosphate. Acta Crystallogr D Biol Crystallogr. 2010 Jul;66(Pt 7):843-9. Epub 2010 Jun 19. PMID:20606265 doi:10.1107/S0907444910019621
↑ Pellegrini O, Nezzar J, Marchfelder A, Putzer H, Condon C. Endonucleolytic processing of CCA-less tRNA precursors by RNase Z in Bacillus subtilis. EMBO J. 2003 Sep 1;22(17):4534-43. PMID:12941704 doi:http://dx.doi.org/10.1093/emboj/cdg435
↑ Sylvester ID, Roberts LM, Lord JM. Characterization of prokaryotic recombinant Aspergillus ribotoxin alpha-sarcin. Biochim Biophys Acta. 1997 Aug 21;1358(1):53-60. PMID:9296521
↑ Datta AK, Niyogi K. A novel oligoribonuclease of Escherichia coli. II. Mechanism of action. J Biol Chem. 1975 Sep 25;250(18):7313-9. PMID:170260
↑ Yehudai-Resheff S, Hirsh M, Schuster G. Polynucleotide phosphorylase functions as both an exonuclease and a poly(A) polymerase in spinach chloroplasts. Mol Cell Biol. 2001 Aug;21(16):5408-16. PMID:11463823 doi:http://dx.doi.org/10.1128/MCB.21.16.5408-5416.2001
↑ Dudkina E, Kayumov A, Ulyanova V, Ilinskaya O. New insight into secreted ribonuclease structure: binase is a natural dimer. PLoS One. 2014 Dec 31;9(12):e115818. doi: 10.1371/journal.pone.0115818., eCollection 2014. PMID:25551440 doi:http://dx.doi.org/10.1371/journal.pone.0115818
↑ Hirayama T, Matsuura T, Ushiyama S, Narusaka M, Kurihara Y, Yasuda M, Ohtani M, Seki M, Demura T, Nakashita H, Narusaka Y, Hayashi S. A poly(A)-specific ribonuclease directly regulates the poly(A) status of mitochondrial mRNA in Arabidopsis. Nat Commun. 2013;4:2247. doi: 10.1038/ncomms3247. PMID:23912222 doi:http://dx.doi.org/10.1038/ncomms3247
↑ Schmier BJ, Nelersa CM, Malhotra A. Structural Basis for the Bidirectional Activity of Bacillus nanoRNase NrnA. Sci Rep. 2017 Sep 11;7(1):11085. doi: 10.1038/s41598-017-09403-x. PMID:28894100 doi:http://dx.doi.org/10.1038/s41598-017-09403-x
↑ Lai LB, Chan PP, Cozen AE, Bernick DL, Brown JW, Gopalan V, Lowe TM. Discovery of a minimal form of RNase P in Pyrobaculum. Proc Natl Acad Sci U S A. 2010 Dec 28;107(52):22493-8. PMID:21135215 doi:10.1073/pnas.1013969107
↑ OLSON BH, GOERNER GL. ALPHA SARCIN, A NEW ANTITUMOR AGENT. I. ISOLATION, PURIFICATION, CHEMICAL COMPOSITION, AND THE IDENTITY OF A NEW AMINO ACID. Appl Microbiol. 1965 May;13:314-21. PMID:14325268
↑ Makarov AA, Kolchinsky A, Ilinskaya ON. Binase and other microbial RNases as potential anticancer agents. Bioessays. 2008 Aug;30(8):781-90. doi: 10.1002/bies.20789. PMID:18623073 doi:http://dx.doi.org/10.1002/bies.20789
↑ Becknell B, Eichler TE, Beceiro S, Li B, Easterling RS, Carpenter AR, James CL, McHugh KM, Hains DS, Partida-Sanchez S, Spencer JD. Ribonucleases 6 and 7 have antimicrobial function in the human and murine urinary tract. Kidney Int. 2015 Jan;87(1):151-61. doi: 10.1038/ki.2014.268. Epub 2014 Jul 30. PMID:25075772 doi:http://dx.doi.org/10.1038/ki.2014.268
↑ Scherbik SV, Paranjape JM, Stockman BM, Silverman RH, Brinton MA. RNase L plays a role in the antiviral response to West Nile virus. J Virol. 2006 Mar;80(6):2987-99. PMID:16501108 doi:http://dx.doi.org/10.1128/JVI.80.6.2987-2999.2006
↑ Kobayashi H, Motoyoshi N, Itagaki T, Tabata K, Suzuki T, Inokuchi N. The inhibition of human tumor cell proliferation by RNase Pol, a member of the RNase T1 family, from Pleurotus ostreatus. Biosci Biotechnol Biochem. 2013;77(7):1486-91. Epub 2013 Jul 7. PMID:23832341 doi:http://dx.doi.org/10.1271/bbb.130133
↑ Thorn A, Steinfeld R, Ziegenbein M, Grapp M, Hsiao HH, Urlaub H, Sheldrick GM, Gartner J, Kratzner R. Structure and activity of the only human RNase T2. Nucleic Acids Res. 2012 Jun 26. PMID:22735700 doi:10.1093/nar/gks614
↑ Acquati F, Lualdi M, Bertilaccio S, Monti L, Turconi G, Fabbri M, Grimaldi A, Anselmo A, Inforzato A, Collotta A, Cimetti L, Riva C, Gribaldo L, Ghia P, Taramelli R. Loss of function of Ribonuclease T2, an ancient and phylogenetically conserved RNase, plays a crucial role in ovarian tumorigenesis. Proc Natl Acad Sci U S A. 2013 May 14;110(20):8140-5. doi:, 10.1073/pnas.1222079110. Epub 2013 Apr 29. PMID:23630276 doi:http://dx.doi.org/10.1073/pnas.1222079110
↑ Birdsall DL, McPherson A. Crystal structure disposition of thymidylic acid tetramer in complex with ribonuclease A. J Biol Chem. 1992 Nov 5;267(31):22230-6. PMID:1429575