History of RNase P and Overview of Its Catalytic Activity

  • Sidney Altman
Part of the Protein Reviews book series (PRON, volume 10)


A description of the history of RNase P, including a few of the personal events in the experimental process, is given. The discovery of the catalytic action of the RNA subunit of RNase P from Escherichia coli is also presented in some detail.


Protein Subunit Glycerol Gradient Human RNase tRNA Precursor Computer Assisted Model 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The author thanks profusely all the members of his own laboratory over the years who have contributed their experimental efforts and perceptive discussions that formulated the results from Yale University. The author also thanks Rose Stone for sterling service as an administrative assistant over a period of many years.


  1. Altman S (1971) Isolation of tyrosine tRNA precursor molecules. Nat New Biol 229:19–21CrossRefPubMedGoogle Scholar
  2. Altman S, Smith JD (1971) Tyrosine tRNA precursor molecule polynucleotide sequence. Nat New Biol 233:35–39PubMedGoogle Scholar
  3. Andrews AJ, Hall TA, Brown JW (2001) Characterization of RNase P holoenzyme from Methanococcus jannaschi and Methanothermobacter thermoautotrophicus. Biol Chem 382:1171–1177CrossRefPubMedGoogle Scholar
  4. Avery OT, MacLeod CM, McCarty M (1944) Studies of the chemical nature of the substance inducing transformation of pneumonococal types. J Exp Med 79:137–158CrossRefPubMedGoogle Scholar
  5. Baer MF, Wesolowski D, Altman S (1989) Characterization in vitro of the defect in a temperature sensitive mutant of the protein subunit of ribonuclease P from Escherichia coli. J Bacteriol 171:6862–6866PubMedGoogle Scholar
  6. Bai Y, Trang P, Li H, Kim K, Zhou T, Liu F (2008) Effective inhibition in animals of viral pathogenesis by ribozyme derived from RNase P catalytic RNA. Proc Natl Acad Sci U S A 105:10919–10924CrossRefPubMedGoogle Scholar
  7. Bartkiewicz M, Gold H, Altman S (1989) Identification and characterization of an RNA molecule that copurifies with RNase P activity from HeLa cells. Genes Dev 3:488–499CrossRefPubMedGoogle Scholar
  8. Bikoff EK, LaRue BF, Gefter ML (1975) In vitro synthesis of transfer RNA. J Biol Chem 250:6248–6255PubMedGoogle Scholar
  9. Boomershine WP, McElroy CA, Tsai H, Wilson RC, Gopalan V, Foster MP (2003) Structure of Mth11/Mth Rpp 29, an essential protein subunit of archaeal and eukaryotic RNase P. Proc Natl Acad Sci U S A 100:15398–15403CrossRefPubMedGoogle Scholar
  10. Bothwell ALM, Altman S (1975) Partial purification and properties of an endoribonclease indicated from human ICIS cells. J Biol Chem 250:1451–1459PubMedGoogle Scholar
  11. Bothwell ALM, Garber R, Altman S (1976) Isolation and nucleotide sequence of precursor molecules to E. coli 4.5 S RNA. J Biol Chem 251:7709–7716PubMedGoogle Scholar
  12. Burdon RH (1975) Processing of tRNA precursors in higher organisms. Brookhaven Symp Biol 26:138–153PubMedGoogle Scholar
  13. Chamberlain JR, Pagan-Ramos E, Kindelberger DW, Engelke DR (1996) An RNase P RNA subunit mutation affects ribosomal RNA processing. Nucleic Acids Res 24:3158–3166CrossRefPubMedGoogle Scholar
  14. Chen JL, Nolan JM, Harris ME, Pace NR (1998) Comparative photocross-linking analysis of the tertiary structures of Escherichia coli and Bacillus subtilis RNase P RNASs. EMBO J 17:1515–1525CrossRefPubMedGoogle Scholar
  15. Coughlin DJ, Pleiss JA, Walker SC, Whitworth GB, Engelke DR (2008) Proc Natl Acad Sci U S A 105:12218–12223CrossRefPubMedGoogle Scholar
  16. Darr SC, Brown JW, Pace NR (1992) The varieties of ribonclease P. Trends Biochem Sci 17:178–182CrossRefPubMedGoogle Scholar
  17. Eder PS, Kekuda R, Stolc V, Altman S (1997) Characterization of two scleroderma autoimmune antigens that copurify with human ribonuclease P. Proc Natl Acad Sci U S A 94:1101–1106CrossRefPubMedGoogle Scholar
  18. Forster AC, Altman S (1990) External guide sequences for an RNA enzyme. Science 249:783–786CrossRefPubMedGoogle Scholar
  19. Gardiner KJ, Marsh TL, Pace NR (1985) Ion dependence of the B. subtilis RNase P reaction. J Biol Chem 260:5415–5419PubMedGoogle Scholar
  20. Gopalan V, Vioque A, Altman S (2002) RNase P: variations and uses. J Biol Chem 277:6759–6762CrossRefPubMedGoogle Scholar
  21. Greenleaf WF, Frieda KL, Foster DA, Woodside MT, Block SM (2008) Direct observation of hierarchical folding in single riboswitch optamers. Science 319:630–633CrossRefPubMedGoogle Scholar
  22. Guerrier-Takada C, Altman S (1992) Reconstitution of enzymatic activity from fragments of M1 RNA. Proc Natl Acad Sci U S A 89:1266–1270CrossRefPubMedGoogle Scholar
  23. Guerrier-Takada C, Gardiner K, Marsh T, Pace NR, Altman S (1983) The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell 35:849–857CrossRefPubMedGoogle Scholar
  24. Guerrier-Takada C, Haydock K, Allen L, Altman S (1986) Metal ion requirements and other aspects of the reaction catalyzed by M1 RNA, the RNA subunit of ribonuclease P from Escherichia coli. Biochemistry 25:1509–1515CrossRefPubMedGoogle Scholar
  25. Guerrier-Takada C, van Belkum A, Pleij CWA, Altman S (1988) Novel reactions of RNase P with tRNA-like structures in turnip yellow mosaic virus RNA. Cell 53:267–272CrossRefPubMedGoogle Scholar
  26. Guerrier-Takada C, Li Y, Altman S (1995) Artificial regulation of gene expression in Escherichia coli by RNase P. Proc Natl Acad Sci U S A 92:11115–11119CrossRefPubMedGoogle Scholar
  27. Guerrier-Takada C, Salavati R, Altman S (1997) Phenotypic conversion of drug-resistant bacteria to drug sensitivity. Proc Natl Acad Sci U S A 94:8468–8472CrossRefPubMedGoogle Scholar
  28. Guthrie C, Seidman JG, Altman S, McClain WH, Smith JD, Barrell BG (1973) Identification of transfer RNA precursor molecules made by bacteriophage T4. Nat New Biol 246:6–11PubMedGoogle Scholar
  29. Hansen FG, Hansen EB, Atlung T (1985) Physical mapping and nucleotide sequence of the rnpA gene that encodes the protein component of ribonuclease P in Escherichia coli. Gene 38:85–93CrossRefPubMedGoogle Scholar
  30. Haydock K, Allen LC (1985) Molecular mechanism of catalysis by RNA. Prog Clin Biol Res 172A:87–98PubMedGoogle Scholar
  31. Holzmann J, Frank P, Loffler E, Bennett KL, Gerner C, Rossmanith W (2008) RNase P without RNA: identification and functional reconstitution of the human mitochondrial tRNA processing enzyme. Cell 135:462–474CrossRefPubMedGoogle Scholar
  32. James BD, Olsen GJ, Liu JS, Pace NR (1988) The secondary structure of ribonuclease P RNA, the catalytic element of a ribonucleoprotein enzyme. Cell 52:19–26CrossRefPubMedGoogle Scholar
  33. Jarrous N, Altman S (2001) Human ribonuclease P. Methods Enzymol 342:93–100CrossRefPubMedGoogle Scholar
  34. Jarrous N, Wolenski JS, Wesolowski D, Lee C, Altman S (1999) Localization in the nucleolus and coiled bodies of protein subunits of the ribonucleoprotein ribonuclease P. J Cell Biol 146:559–571CrossRefPubMedGoogle Scholar
  35. Jiang T, Altman S (2001) Protein-protein interactions with subunits of human nuclear RNase P. Proc Natl Acad Sci U S A 98:920–925CrossRefPubMedGoogle Scholar
  36. Jiang T, Altman S (2002) A protein subunit of human RNase P, Rpp 14, and its interacting partner, OIP2, have 3′→5′ exoribonuclease activity. Proc Natl Acad Sci U S A 99:5295–5300CrossRefPubMedGoogle Scholar
  37. Jiang T, Guerrier-Takada C, Altman S (2001) Protein–RNA interactions in the subunits of human nuclear RNase P. RNA 7:937–941CrossRefPubMedGoogle Scholar
  38. Kazakov S, Altman S (1991) Site-specific cleavage by metal ion cofactors and inhibitors of M1 RNA, the catalytic subunit of RNase P from E. coli. Proc Natl Acad Sci U S A 88:9193–9197CrossRefPubMedGoogle Scholar
  39. Kazantsev AV, Krivenko AA, Harrington DJ, Carter RJ, Holbrook SR, Adams PD, Pace NR (2003) High-resolution structure of RNase P protein from Thermotoga maritima. Proc Natl Acad Sci U S A 100:7497–7502CrossRefPubMedGoogle Scholar
  40. Kazantsev AV, Krivenko AA, Harrington DJ, Holbrook SR, Adams PD, Pace NR (2005) Crystal structure of a bacterial ribonuclease P RNA. Proc Natl Acad Sci U S A 102:13392–13397CrossRefPubMedGoogle Scholar
  41. Kikovska E, Svard SG, Kirsebom LA (2007) Eukaryotic RNase P mediates cleavage in the absence of protein. Proc Natl Acad Sci U S A 104:2062–2067CrossRefPubMedGoogle Scholar
  42. Kim K, Umamoto S, Trang P, Hai R, Liu F (2004) Intracellular expression of engineered RNase P ribozymes effectively blocks gene expression and replication of human cytomegalovirus. RNA 10:438–447CrossRefPubMedGoogle Scholar
  43. Ko JH, Izadjoo M, Altman S (2008) Inhibition of expression of virulence genes of Yersinia pestis in Escherichia coli by external guide sequences and RNase P. RNA 14:1656–1662CrossRefPubMedGoogle Scholar
  44. Kole R, Altman S (1981) Properties of purified RNase P from E. coli. Biochemistry 20:1902–1906CrossRefPubMedGoogle Scholar
  45. Komine Y, Kitibataka M, Yokogawa T, Nishikawa K, Inokuchi H (1999) A tRNA-like structure is present in l0Sa RNA, a small stable RNA from Escherichia coli. Proc Natl Acad Sci U S A 91:9223–9227CrossRefGoogle Scholar
  46. Koski R, Bothwell ALM, Altman S (1976) Partial purification and characterization of a ribonucleasse P-like activity from human KB cells. Cell 9:101–116CrossRefPubMedGoogle Scholar
  47. Kouzuma Y, Mizoguchi M, Takagi H, Fukuhara H, Tsukamoto M, Numata T, Kimura M (2003) Reconstitution of archaeal ribonuclease P from RNA and four protein components. Biochem Biophys Res Commun 306:666–673CrossRefPubMedGoogle Scholar
  48. Kovrigina E, Wesolowski D, Altman S (2003) Coordinate inhibition of expression of several genes for protein subunits of human nuclear RNase P. Proc Natl Acad Sci U S A 100:1598–1602CrossRefPubMedGoogle Scholar
  49. Krasilnikov AS, Yang X, Pan T, Mondragon T (2003) Crystal structure of the specificity domain of ribonuclease P. Nature 421:760–764CrossRefPubMedGoogle Scholar
  50. Kraus G, Geffin R, Spruill G, Young AK, Seivright R, Cardona D, Burzawa J, Hnatyszyn HJ (2002) Cross-clade inhibition of HIV-1 replication and cytopathology using sequence-specific RNase P molecules. Proc Natl Acad Sci U S A 99:3406–3411CrossRefPubMedGoogle Scholar
  51. Li Y, Altman S (2003) A specific endoribonuclease RNase P, affects gene expression in polycistronic operon mRNAs. Proc Natl Acad Sci U S A 100:13213–13218CrossRefPubMedGoogle Scholar
  52. Li Y, Altman S (2004) Polarity effects in the lac operon of E. coli. J Mol Biol 339:31–39CrossRefPubMedGoogle Scholar
  53. Liu F, Altman S (1995) Inhibition of viral gene expression by the catalytic RNA subunit of RNase P from Escherichia coli. Genes Dev 9:471–480CrossRefPubMedGoogle Scholar
  54. Mann H, Ben-Asouli Y, Schien A, Moussa S, Jarrous N (2003) Eukaryotic RNase P: role of RNA and protein subunits of a primordial catalytic ribonucleoprotein in RNA-based catalysis. Mol Cell 12:925–935CrossRefPubMedGoogle Scholar
  55. McKinney J, Guerrier-Takada C, Wesolowski D, Altman S (2001) Inhibition of Escherichia coli viability by 221 external guide sequences complementary to two essential genes. Proc Natl Acad Sci U S A 98:6605–6610CrossRefPubMedGoogle Scholar
  56. Ozeki H, Sakano H, Youada S, Ikemura T, Shimura Y (1975) Temperature sensitive mutants of Escherichia coli defective in tRNA biosynthesis. Brookhaven Symp 26:89–105Google Scholar
  57. Pannucci JA, Haas ES, Hall TA, Harris JK, Brown JW (1999) RNase P RNAs from some Archaea are catalytically active. Proc Nat Acad Sci U S A 96:7803–7808CrossRefGoogle Scholar
  58. Peck-Miller K, Altman S (1991) Kinetics of the processing of the precursor to 4.5 S RNA, a naturally occurring substrate for RNase P from E. coli. J Mol Biol 221:1–5CrossRefPubMedGoogle Scholar
  59. Pei D-S, Sun Y-H, Long Y, Zhu Z-Y (2008) Inhibition of no tail (ntl) gene expression in zebrafish by external guide sequence (EGS) technique. Mol Biol Rep 35:139–143CrossRefPubMedGoogle Scholar
  60. Persson T, Cuzic S, Hartmann RK (2003) Catalysis by RNase P RNA: unique features and unprecedented active site plasticity. J Biol Chem 278:43394–435401CrossRefPubMedGoogle Scholar
  61. Plehn-Dujowich D, Altman S (1998) Effective inhibition of influenza virus production in cultured cells by external guide sequences and ribonuclease P. Proc Natl Acad Sci U S A 95:7327–7332CrossRefPubMedGoogle Scholar
  62. Puranam RS, Attardi G (2001) The RNase P associated with HeLa cell mitochondria contains an essential RNA component identical in sequence to that of nuclear RNase P. Mol Cell Biol 21:548–561CrossRefPubMedGoogle Scholar
  63. Rangarajan S, Raj ML, Hernandez JM, Grotewold E, Gopalan V (2004) RNase P as a tool for disruption of gene expression in maize cells. Biochem J 380:611–616CrossRefPubMedGoogle Scholar
  64. Reiner R, BenAsouli Y, Krivetsky I, Jarrous N (2006) A role for the catalytic riboneucleoprotein in RNA polymerase III transcription. Genes Dev 20:1621–1635CrossRefPubMedGoogle Scholar
  65. Rendan L, Schroder I, Soll D (2008) Life without RNase P. Nature 453:120–123CrossRefGoogle Scholar
  66. Robertson HD, Altman S, Smith JD (1972) Purification and properties of a specific Escherichia coli ribonuclease which cleaves a tyrosine transfer ribonucleic acid precursor. J Biol Chem 247:5243–5251PubMedGoogle Scholar
  67. Rossmanith W, Karwan RM (1998) Characterization of human mitochondrial RNase P: novel aspects in tRNA processing. Biochem Biophys Res Commun 247:234–241CrossRefPubMedGoogle Scholar
  68. Samanta MP, Tongprasit W, Sethi H, Chin CS, Stolc V (2006) Global identification of noncoding RNAs in Sacchaaromyces cerevisiae by modulating an essential RNA processing pathway. Proc Natl Acad Sci U S A 103:4192–4197CrossRefPubMedGoogle Scholar
  69. Schedl P, Primakoff P (1973) Mutants of Escherichia coli thermosensitive for the synthesis of transfer RNA. Proc Natl Acad Sci U S A 70:2091–2095CrossRefPubMedGoogle Scholar
  70. Seif E, Altman S (2008) RNase P cleaves the adenine riboswitch and stabilizes pbuE mRNA in B. subtilis. RNA 14:1237–1243CrossRefPubMedGoogle Scholar
  71. Shan G, personal communicationGoogle Scholar
  72. Spitzfaden C, Nicholson N, Jones JJ, Guth S, Lehr R, Prescott CD, Hegg LA, Eggleston DS (2000) The structure of ribonuclease P protein from Staphylococcus aureus reveals a unique binding site for single-stranded RNA. J Mol Biol 295(1):105–115CrossRefPubMedGoogle Scholar
  73. Stams TS, Niranjanakumari S, Fierke CA, Christianson DW (1998) Ribonuclease P protein structure: evolutionary origins in the translational apparatus. Science 280:752–755CrossRefPubMedGoogle Scholar
  74. Stark BC, Kole R, Bowman EJ, Altman S (1978) Ribonuclease P: an enzyme with an essential RNA component. Proc Natl Acad Sci U S A 75:3717–3721CrossRefPubMedGoogle Scholar
  75. Steitz TA, Moore PB (2003) RNA, the first macromolecular catalyst: the ribosome is a ribozyme. Trends Biochem Sci 28:411–418CrossRefPubMedGoogle Scholar
  76. Stolc V, Altman S (1997) Rpp 1, an essential protein subunit of nuclear RNase P required for processing of precursor tRNA and 35 S precursor rRNA in Saccharomyces cerevisiae. Genes Dev 11:2414–2425CrossRefPubMedGoogle Scholar
  77. Tsai HY, Masquida B, Biswas R, Westhof E, Gopalan V (2003) Molecular modeling of the three-dimensional structure of the bacterial RNase P holoenzyme. J Mol Biol 325:661–675CrossRefPubMedGoogle Scholar
  78. Tsai HY, Pulukkunat DK, Woznick WK, Gopalan V (2006) Functional reconstitution and characterization of Pyrococcus furiosus RNase P. Proc Natl Acad Sci U S A 103:16147–16152CrossRefPubMedGoogle Scholar
  79. Wang MJ, Davis NW, Gegenheimer P (1988) Novel mechanisms for maturation of chloroplast transfer RNA precursors. EMBO J 7:1567–1574PubMedGoogle Scholar
  80. Waugh DS, Pace NR (1990) Complementation of an RNase P (rnpB) glue deletion in Escherichia coli by homologous genes from distantly related bacteria. J Bacteriol 172:6316–6322PubMedGoogle Scholar
  81. Westhof E, Wesolowski D, Altman S (1996) Mapping in three dimensions of regions in a catalytic RNA protected from attack by an FE(II)-EDTA reagent. J Mol Biol 258:600–613CrossRefPubMedGoogle Scholar
  82. Yang L, Altman S (2007) A non-coding RNA in Saccharomyces cerivisiae is a RNase P substrate. RNA 13:1–9Google Scholar
  83. Zahler NH, Sun L, Christian EL, Harris ME (2005) The pre-tRNA nucleotide base and 2′-hydroxyl at N-1 contribute to fidelity in tRNA processing by RNase P. J Mol Biol 345:969–985CrossRefPubMedGoogle Scholar
  84. Zhang H, Altman S (2004) Inhibition of the expression of the human RNase P protein subunits Rpp 21, Rpp25, Rpp29 by external guide sequences (EGSs) and siRNA. J Mol Biol 342:1077–1083CrossRefPubMedGoogle Scholar
  85. Zuo Y, Deutscher MP (2002) Mechanism and action of RNase T. J Biol Chem 277:50160–50164CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Molecular, Cellular and Developmental BiologyYale UniversityNew HavenUSA

Personalised recommendations