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.
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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.
Coordinates and structure factors have been deposited in the Protein Data Bank under the accession code 2A2E. Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.
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Torres-Larios, A., Swinger, K., Krasilnikov, A. et al. Crystal structure of the RNA component of bacterial ribonuclease P. Nature 437, 584–587 (2005). https://doi.org/10.1038/nature04074
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