Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Crystal structure of the RNA component of bacterial ribonuclease P


Transfer RNA (tRNA) is produced as a precursor molecule that needs to be processed at its 3′ and 5′ ends. Ribonuclease P is the sole endonuclease responsible for processing the 5′ end of tRNA by cleaving the precursor and leading to tRNA maturation. It was one of the first catalytic RNA molecules identified1 and consists of a single RNA component in all organisms and only one protein component in bacteria. It is a true multi-turnover ribozyme and one of only two ribozymes (the other being the ribosome) that are conserved in all kingdoms of life. Here we show the crystal structure at 3.85 Å resolution of the RNA component of Thermotoga maritima ribonuclease P. The entire RNA catalytic component is revealed, as well as the arrangement of the two structural domains. The structure shows the general architecture of the RNA molecule, the inter- and intra-domain interactions, the location of the universally conserved regions, the regions involved in pre-tRNA recognition and the location of the active site. A model with bound tRNA is in agreement with all existing data and suggests the general basis for RNA–RNA recognition by this ribozyme.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Schematic diagram of T. maritima RNase P RNA.
Figure 2: Conserved and interacting regions in RNase P.
Figure 3: Model of RNase P–tRNA interactions.


  1. Guerrier-Takada, C., Gardiner, K., Marsh, T., Pace, N. & Altman, S. The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell 35, 849–857 (1983)

    CAS  Article  Google Scholar 

  2. Christian, E. L., Zahler, N. H., Kaye, N. M. & Harris, M. E. Analysis of substrate recognition by the ribonucleoprotein endonuclease RNase P. Methods 28, 307–322 (2002)

    CAS  Article  Google Scholar 

  3. McClain, W. H., Guerrier-Takada, C. & Altman, S. Model substrates for an RNA enzyme. Science 238, 527–530 (1987)

    ADS  CAS  Article  Google Scholar 

  4. Kirsebom, L. A. & Svard, S. G. Base pairing between Escherichia coli RNase P RNA and its substrate. EMBO J. 13, 4870–4876 (1994)

    CAS  Article  Google Scholar 

  5. Christian, E. L., Kaye, N. M. & Harris, M. E. Evidence for a polynuclear metal ion binding site in the catalytic domain of ribonuclease P RNA. EMBO J. 21, 2253–2262 (2002)

    CAS  Article  Google Scholar 

  6. Beebe, J. A., Kurz, J. C. & Fierke, C. A. Magnesium ions are required by Bacillus subtilis ribonuclease P RNA for both binding and cleaving precursor tRNAAsp. Biochemistry 35, 10493–10505 (1996)

    CAS  Article  Google Scholar 

  7. Perreault, J. P. & Altman, S. Pathway of activation by magnesium ions of substrates for the catalytic subunit of RNase P from Escherichia coli. J. Mol. Biol. 230, 750–756 (1993)

    CAS  Article  Google Scholar 

  8. Smith, D. & Pace, N. R. Multiple magnesium ions in the ribonuclease P reaction mechanism. Biochemistry 32, 5273–5281 (1993)

    CAS  Article  Google Scholar 

  9. Kurz, J. C. & Fierke, C. A. Ribonuclease P: a ribonucleoprotein enzyme. Curr. Opin. Chem. Biol. 4, 553–558 (2000)

    CAS  Article  Google Scholar 

  10. Pannucci, J. A., Haas, E. S., Hall, T. A., Harris, J. K. & Brown, J. W. RNase P RNAs from some Archaea are catalytically active. Proc. Natl Acad. Sci. USA 96, 7803–7808 (1999)

    ADS  CAS  Article  Google Scholar 

  11. Reich, C., Olsen, G. J., Pace, B. & Pace, N. R. Role of the protein moiety of ribonuclease P, a ribonucleoprotein enzyme. Science 239, 178–181 (1988)

    ADS  CAS  Article  Google Scholar 

  12. Loria, A. & Pan, T. Domain structure of the ribozyme from eubacterial ribonuclease P. RNA 2, 551–563 (1996)

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Krasilnikov, A. S., Yang, X., Pan, T. & Mondragón, A. Crystal structure of the specificity domain of ribonuclease P. Nature 421, 760–764 (2003)

    ADS  CAS  Article  Google Scholar 

  14. Krasilnikov, A. S., Xiao, Y., Pan, T. & Mondragón, A. Basis for structural diversity in homologous RNAs. Science 306, 104–107 (2004)

    ADS  CAS  Article  Google Scholar 

  15. Chen, J.-L. & Pace, N. R. Identification of the universally conserved core of ribonuclease P RNA. RNA 3, 557–560 (1997)

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Massire, C., Jaeger, L. & Westhof, E. Derivation of the three-dimensional architecture of bacterial ribonuclease P RNAs from comparative sequence analysis. J. Mol. Biol. 279, 773–793 (1998)

    CAS  Article  Google Scholar 

  17. Harris, M. E. et al. Use of photoaffinity crosslinking and molecular modeling to analyse the global architecture of ribonuclease P RNA. EMBO J. 13, 3953–3963 (1994)

    CAS  Article  Google Scholar 

  18. Guerrier-Takada, C. & Altman, S. Reconstitution of enzymatic activity from fragments of M1 RNA. Proc. Natl Acad. Sci. USA 89, 1266–1270 (1992)

    ADS  CAS  Article  Google Scholar 

  19. Harris, M. E., Kazantsev, A. V., Chen, J. L. & Pace, N. R. Analysis of the tertiary structure of the ribonuclease P ribozyme-substrate complex by site-specific photoaffinity crosslinking. RNA 3, 561–576 (1997)

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Brown, J. W. et al. Comparative analysis of ribonuclease P RNA using gene sequences from natural microbial populations reveals tertiary structural elements. Proc. Natl Acad. Sci. USA 93, 3001–3006 (1996)

    ADS  CAS  Article  Google Scholar 

  21. Massire, C., Jaeger, L. & Westhof, E. Phylogenetic evidence for a new tertiary interaction in bacterial RNase P RNAs. RNA 3, 553–556 (1997)

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Siegel, R. W., Banta, A. B., Haas, E. S., Brown, J. W. & Pace, N. R. Mycoplasma fermentans simplifies our view of the catalytic core of ribonuclease P RNA. RNA 2, 452–462 (1996)

    CAS  PubMed  PubMed Central  Google Scholar 

  23. LaGrandeur, T. E., Huttenhofer, A., Noller, H. F. & Pace, N. R. Phylogenetic comparative chemical footprint analysis of the interaction between ribonuclease P RNA and tRNA. EMBO J. 13, 3945–3952 (1994)

    CAS  Article  Google Scholar 

  24. Odell, L., Huang, V., Jakacka, M. & Pan, T. Interaction of structural modules in substrate binding by the ribozyme from Bacillus subtilis RNase P. Nucleic Acids Res. 26, 3717–3723 (1998)

    CAS  Article  Google Scholar 

  25. Loria, A. & Pan, T. Recognition of the T stem-loop of a pre-tRNA substrate by the ribozyme from Bacillus subtilis ribonuclease P. Biochemistry 36, 6317–6325 (1997)

    CAS  Article  Google Scholar 

  26. Zahler, N. H., Christian, E. L. & Harris, M. E. Recognition of the 5′ leader of pre-tRNA substrates by the active site of ribonuclease P. RNA 9, 734–745 (2003)

    CAS  Article  Google Scholar 

  27. Tsai, H. Y., Masquida, B., Biswas, R., Westhof, E. & Gopalan, V. Molecular modeling of the three-dimensional structure of the bacterial RNase P holoenzyme. J. Mol. Biol. 325, 661–675 (2003)

    CAS  Article  Google Scholar 

  28. delaFortelle, E. & Bricogne, G. Maximum-likelihood heavy-atom parameter refinement for multiple isomorphous replacement and multiwavelength anomalous diffraction methods. Methods Enzymol. 276, 472–494 (1997)

    CAS  Article  Google Scholar 

  29. Murshudov, G. N., Vagin, A. A. & Dodson, E. J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D 53, 240–255 (1997)

    CAS  Article  Google Scholar 

  30. Brunger, A. T. et al. Crystallography & NMR system: A new software suite for macromolecular structure determination. Acta Crystallogr. D 54, 905–921 (1998)

    CAS  Article  Google Scholar 

Download references


We thank M. Yusupov, B. Golden and J. Cate for their gift of osmium and iridium hexamine, and Y. Zhang for mass spectrometry. We thank A.-C. Dock-Bregeon, E. Sontheimer and O. Uhlenbeck for comments and suggestions, P. Nissen for advice and A. Vega-Miranda for help with the figures. Research was supported by an NIH grant to A.M. Support from the R.H. Lurie Cancer Center of Northwestern University to the Structural Biology Center is acknowledged. Portions of this work were performed at the DND, LS, IMCA and SER Collaborative Access Teams at the Advanced Photon Source. We thank members of these teams for their help and support. DND-CAT is supported by DuPont, Dow, and the NSF, and use of the Advanced Photon Source is supported by the DOE.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Alfonso Mondragón.

Ethics declarations

Competing interests

Coordinates and structure factors have been deposited in the Protein Data Bank under the accession code 2A2E. Reprints and permissions information is available at The authors declare no competing financial interests.

Supplementary information

Supplementary Notes

This file contains Supplementary Methods, Supplementary Figures S1–S5, Supplementary Table S1 and additional references. (PDF 2938 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Torres-Larios, A., Swinger, K., Krasilnikov, A. et al. Crystal structure of the RNA component of bacterial ribonuclease P. Nature 437, 584–587 (2005).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing