Skip to main content

Thank you for visiting nature.com. 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.

  • Article
  • Published:

The identification and characterization of a selected SAM-dependent methyltransferase ribozyme that is present in natural sequences

Nature Catalysis volume 4, pages 872–881 (2021)Cite this article

Subjects

Abstract

RNA methylations contribute to a wide range of cellular functions. Cellular RNAs are usually methylated by protein methyltransferases using S-adenosyl-l-methionine (SAM) as a cofactor. Here we report the in vitro selection of a 33-nucleotide SAM-dependent methyltransferase ribozyme RNA from a randomized sequence. Detection and mapping of the methyl group on the RNA demonstrates site-specific methylation of the N7 position of guanine by SAM. The ribozyme is active over a wide range of pH and temperatures and is robust compared to protein enzymes. The ribozyme structures in the presence and absence of SAM show a dramatic local conformational change associated with cofactor binding. The ribozyme motif was found to be distributed in nature, and candidate sequences were shown to be active in vitro. The discovery of this ribozyme that uses the cofactor SAM to specifically methylate RNA opens up the possibility that methyltransferase ribozymes may contribute to cellular RNA methylation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Detection of m7G methylation.
Fig. 2: Characterization of the ribozyme methyltransferase.
Fig. 3: The crystal structure of SMRZ-1 ribozyme.
Fig. 4: Distribution of candidate methyltransferase ribozyme sequences.

Similar content being viewed by others

Data availability

The data supporting the findings of this study are available within the paper (and its supplementary information files and source data files). Structural factors and coordinates of the SMRZ-1 RNA–U1A protein complex have been deposited in the Protein Data Bank under accession codes 7DLZ and 7DWH for the SMRZ-1 RNA–U1A complex in the absence and presence of SAM, respectively. Source data are provided with this paper.

Code availability

The script for searching the Refseq genomic database is available at: https://github.com/threadtag/SMRZ-1.

References

  1. Roundtree, I. A., Evans, M. E., Pan, T. & He, C. Dynamic RNA modifications in gene expression regulation. Cell 169, 1187–1200 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Benne, R. & Grosjean, H. Modification and Editing of RNA (American Society for Microbiology, 1998).

  3. Helm, M. & Alfonzo, J. D. Posttranscriptional RNA modifications: playing metabolic games in a cell’s chemical Legoland. Chem. Biol. 21, 174–185 (2014).

    Article  CAS  PubMed  Google Scholar 

  4. Zhang, L.-S. et al. Transcriptome-wide mapping of internal N7-methylguanosine methylome in mammalian mRNA. Mol. Cell 74, 1304–1316.e8 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Pandolfini, L. et al. METTL1 promotes let-7 microRNA processing via m7G methylation. Mol. Cell 74, 1278–1290.e9 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Cantoni, G. L. Biological methylation: selected aspects. Annu. Rev. Biochem. 44, 435–451 (1975).

    Article  CAS  PubMed  Google Scholar 

  7. Loenen, Wa. M. S-Adenosylmethionine: jack of all trades and master of everything? Biochem. Soc. Trans. 34, 330–333 (2006).

    Article  CAS  PubMed  Google Scholar 

  8. Schubert, H. L., Blumenthal, R. M. & Cheng, X. Many paths to methyltransfer: a chronicle of convergence. Trends Biochem. Sci. 28, 329–335 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Traube, F. R. & Carell, T. The chemistries and consequences of DNA and RNA methylation and demethylation. RNA Biol. 14, 1099–1107 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Rydberg, B. & Lindahl, T. Nonenzymatic methylation of DNA by the intracellular methyl group donor S-adenosyl-l-methionine is a potentially mutagenic reaction. EMBO J. 1, 211–216 (1982).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Benner, S. A., Ellington, A. D. & Tauer, A. Modern metabolism as a palimpsest of the RNA world. Proc. Natl Acad. Sci. USA 86, 7054–7058 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Harms, J. et al. High resolution structure of the large ribosomal subunit from a mesophilic eubacterium. Cell 107, 679–688 (2001).

    Article  CAS  PubMed  Google Scholar 

  13. Korostelev, A., Trakhanov, S., Laurberg, M. & Noller, H. F. Crystal structure of a 70S ribosome–tRNA complex reveals functional interactions and rearrangements. Cell 126, 1065–1077 (2006).

    Article  CAS  PubMed  Google Scholar 

  14. Nissen, P., Hansen, J., Ban, N., Moore, P. B. & Steitz, T. A. The structural basis of ribosome activity in peptide bond synthesis. Science 289, 920–930 (2000).

    Article  CAS  PubMed  Google Scholar 

  15. Schuwirth, B. S. et al. Structures of the bacterial ribosome at 3.5 Å resolution. Science 310, 827–834 (2005).

    Article  CAS  PubMed  Google Scholar 

  16. Selmer, M. et al. Structure of the 70S ribosome complexed with mRNA and tRNA. Science 313, 1935–1942 (2006).

    Article  CAS  PubMed  Google Scholar 

  17. Rodnina, M. V. The ribosome as a versatile catalyst: reactions at the peptidyl transferase center. Curr. Opin. Struct. Biol. 23, 595–602 (2013).

    Article  CAS  PubMed  Google Scholar 

  18. Belousoff, M. J. et al. Ancient machinery embedded in the contemporary ribosome. Biochem. Soc. Trans. 38, 422–427 (2010).

    Article  CAS  PubMed  Google Scholar 

  19. 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).

    Article  CAS  PubMed  Google Scholar 

  20. Cech, T. R., Zaug, A. J. & Grabowski, P. J. In vitro splicing of the ribosomal RNA precursor of Tetrahymena: involvement of a guanosine nucleotide in the excision of the intervening sequence. Cell 27, 487–496 (1981).

    Article  CAS  PubMed  Google Scholar 

  21. Peebles, C. L. et al. A self-splicing RNA excises an intron lariat. Cell 44, 213–223 (1986).

    Article  CAS  PubMed  Google Scholar 

  22. van der Veen, R. et al. Excised group II introns in yeast mitochondria are lariats and can be formed by self-splicing in vitro. Cell 44, 225–234 (1986).

    Article  PubMed  Google Scholar 

  23. Prody, G. A., Bakos, J. T., Buzayan, J. M., Schneider, I. R. & Bruening, G. Autolytic processing of dimeric plant virus satellite RNA. Science 231, 1577–1580 (1986).

    Article  CAS  PubMed  Google Scholar 

  24. Buzayan, J. M., Gerlach, W. L. & Bruening, G. Satellite tobacco ringspot virus RNA: a subset of the RNA sequence is sufficient for autolytic processing. Proc. Natl Acad. Sci. USA 83, 8859–8862 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Winkler, W. C., Nahvi, A., Roth, A., Collins, J. A. & Breaker, R. R. Control of gene expression by a natural metabolite-responsive ribozyme. Nature 428, 281–286 (2004).

    Article  CAS  PubMed  Google Scholar 

  26. Tarasow, T. M., Tarasow, S. L. & Eaton, B. E. RNA-catalysed carbon–carbon bond formation. Nature 389, 54–57 (1997).

    Article  CAS  PubMed  Google Scholar 

  27. Kraut, S. et al. Three critical hydrogen bonds determine the catalytic activity of the Diels–Alderase ribozyme. Nucleic Acids Res. 40, 1318–1330 (2012).

    Article  CAS  PubMed  Google Scholar 

  28. Seelig, B. & Jäschke, A. A small catalytic RNA motif with Diels–Alderase activity. Chem. Biol. 6, 167–176 (1999).

    Article  CAS  PubMed  Google Scholar 

  29. Wilson, C. & Szostak, J. W. In vitro evolution of a self-alkylating ribozyme. Nature 374, 777–782 (1995).

    Article  CAS  PubMed  Google Scholar 

  30. Lohse, P. A. & Szostak, J. W. Ribozyme-catalysed amino-acid transfer reactions. Nature 381, 442–444 (1996).

    Article  CAS  PubMed  Google Scholar 

  31. Beaudry, A. A. & Joyce, G. F. Directed evolution of an RNA enzyme. Science 257, 635–641 (1992).

    Article  CAS  PubMed  Google Scholar 

  32. Tjhung, K. F., Shokhirev, M. N., Horning, D. P. & Joyce, G. F. An RNA polymerase ribozyme that synthesizes its own ancestor. Proc. Natl Acad. Sci. USA 117, 2906–2913 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Attwater, J., Wochner, A. & Holliger, P. In-ice evolution of RNA polymerase ribozyme activity. Nat. Chem. 5, 1011–1018 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Attwater, J., Raguram, A., Morgunov, A. S., Gianni, E. & Holliger, P. Ribozyme-catalysed RNA synthesis using triplet building blocks. eLife 7, e35255 (2018).

  35. Scheitl, C. P. M., Ghaem Maghami, M., Lenz, A.-K. & Höbartner, C. Site-specific RNA methylation by a methyltransferase ribozyme. Nature 587, 663–667 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Dominissini, D., Moshitch-Moshkovitz, S., Salmon-Divon, M., Amariglio, N. & Rechavi, G. Transcriptome-wide mapping of N6-methyladenosine by m6A-seq based on immunocapturing and massively parallel sequencing. Nat. Protoc. 8, 176–189 (2013).

    Article  CAS  PubMed  Google Scholar 

  37. Burke, D. H. & Gold, L. RNA aptamers to the adenosine moiety of S-adenosyl methionine: structural inferences from variations on a theme and the reproducibility of SELEX. Nucleic Acids Res. 25, 2020–2024 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Su, D. et al. Quantitative analysis of ribonucleoside modifications in tRNA by HPLC-coupled mass spectrometry. Nat. Protoc. 9, 828–841 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Peattie, D. A. Direct chemical method for sequencing RNA. Proc. Natl Acad. Sci. USA 76, 1760–1764 (1979).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kirpekar, F., Douthwaite, S. & Roepstorff, P. Mapping posttranscriptional modifications in 5S ribosomal RNA by MALDI mass spectrometry. RNA 6, 296–306 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. De Bie, L. G. S. et al. The yggH gene of Escherichia coli encodes a tRNA (m7G46) methyltransferase. J. Bacteriol. 185, 3238–3243 (2003).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Barbés, C., Sánchez, J., Yebra, M. J., Robert-Geró, M. & Hardisson, C. Effects of sinefungin and S-adenosylhomocysteine on DNA and protein methyltransferases from Streptomyces and other bacteria. FEMS Microbiol. Lett. 57, 239–243 (1990).

    Article  PubMed  Google Scholar 

  43. Schluckebier, G., Zhong, P., Stewart, K. D., Kavanaugh, T. J. & Abad-Zapatero, C. The 2.2 Å structure of the rRNA methyltransferase ErmC′ and its complexes with cofactor and cofactor analogs: implications for the reaction mechanism. J. Mol. Biol. 289, 277–291 (1999).

    Article  CAS  PubMed  Google Scholar 

  44. Ferré-D’Amaré, A. R. & Doudna, J. A. Crystallization and structure determination of a hepatitis delta virus ribozyme: use of the RNA-binding protein U1A as a crystallization module. J. Mol. Biol. 295, 541–556 (2000).

    Article  PubMed  CAS  Google Scholar 

  45. Price, I. R., Grigg, J. C. & Ke, A. Common themes and differences in SAM recognition among SAM riboswitches. Biochim. Biophys. Acta 1839, 931–938 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Gruber, A. R., Lorenz, R., Bernhart, S. H., Neuböck, R. & Hofacker, I. L. The Vienna RNA websuite. Nucleic Acids Res. 36, W70–W74 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Wolk, S. K. et al. Modified nucleotides may have enhanced early RNA catalysis. Proc. Natl Acad. Sci. USA 117, 8236–8242 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. White, H. B. Coenzymes as fossils of an earlier metabolic state. J. Mol. Evol. 7, 101–104 (1976).

    Article  CAS  PubMed  Google Scholar 

  49. Laurino, P. & Tawfik, D. S. Spontaneous emergence of S-adenosylmethionine and the evolution of methylation. Angew. Chem. Int. Ed. 56, 343–345 (2017).

    Article  CAS  Google Scholar 

  50. Minor, W., Cymborowski, M., Otwinowski, Z. & Chruszcz, M. HKL-3000: the integration of data reduction and structure solution—from diffraction images to an initial model in minutes. Acta Crystallogr. D Biol. Crystallogr. 62, 859–866 (2006).

    Article  PubMed  CAS  Google Scholar 

  51. McCoy, A. J. Solving structures of protein complexes by molecular replacement with Phaser. Acta Crystallogr. D Biol. Crystallogr. 63, 32–41 (2007).

    Article  CAS  PubMed  Google Scholar 

  52. Potterton, E., Briggs, P., Turkenburg, M. & Dodson, E. A graphical user interface to the CCP4 program suite. Acta Crystallogr. D Biol. Crystallogr. 59, 1131–1137 (2003).

    Article  PubMed  Google Scholar 

  53. Murshudov, G. N. et al. REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr. D Biol. Crystallogr. 67, 355–367 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126–2132 (2004).

    Article  CAS  PubMed  Google Scholar 

  55. Afonine, P. V. et al. Towards automated crystallographic structure refinement with phenix.refine. Acta Crystallogr. D Biol. Crystallogr. 68, 352–367 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Soto, A. M., Gmeiner, W. H. & Marky, L. A. Energetic and conformational contributions to the stability of Okazaki fragments. Biochemistry 41, 6842–6849 (2002).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank members of the Murchie and Gan laboratories for discussion, C. Zhang (IBS, Fudan University) for assistance with LC–MS/MS analysis, X. Zhou (IBS, Fudan University) for assistance with MALDI–TOF mass spectrometry, W. Zhang (Shanghai Jiao Tong University) for assistance with differential scanning calorimetry analysis and the BL19U1 beamline of the National Facility for Protein Science in Shanghai for X-ray diffraction facilities. We also thank the late K. Nagai (MRC Cambridge) for the gift of the U1A expression plasmid. This work was supported by National Key R&D Program of China grant 2016YFA0500604 to A.M., National Natural Science Foundation grants 31420103907, 31770873 and 31330022 to A.M., National Natural Science Foundation grant 31370107 to D.C, Fudan University Original Research Grant 31470777 to H.J. and National Natural Science Foundation of China grant 31870721 to J.G.

Author information

Author notes

  1. These authors contributed equally: H. Jiang, Y. Gao.

Authors and Affiliations

  1. Fudan University Pudong Medical Center, and Shanghai Key Laboratory of Medical Epigenetics, International Laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China

    Hengyi Jiang, Dongrong Chen & Alastair I. H. Murchie

  2. Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China

    Hengyi Jiang, Lei Zhang, Dongrong Chen & Alastair I. H. Murchie

  3. Shanghai Public Health Clinical Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Biochemistry and Biophysics, School of Life Sciences, Fudan University, Shanghai, China

    Yanqing Gao & Jianhua Gan

Authors
  1. Hengyi Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yanqing Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dongrong Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jianhua Gan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alastair I. H. Murchie
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A.I.H.M., D.C. and H.J. were responsible for the initial experimental design. H.J. performed the SELEX and methylation analysis. H.J. and L.Z. performed the mass spectrometry. H.J., Y.G. and J.G. undertook the crystallization and crystallography. Y.G. and J.G. were responsible for structure solution and modelling. H.J. performed the bioinformatic analysis. A.I.H.M., D.C. and J.G. wrote the manuscript.

Corresponding authors

Correspondence to Dongrong Chen, Jianhua Gan or Alastair I. H. Murchie.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information Nature Catalysis thanks Wen Zhang and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data

Extended Data Fig. 1 In vitro selection strategy.

a, Schematic of in vitro selection procedure for the methyltransferase ribozyme. b, Level of radioactivity incorporation for RNAs from round 3 and round 6 after reaction with [methyl-3H] SAM. Error bars are the standard deviation from the mean of 3 independent experiments, data points are shown (as dots).

Source data

Extended Data Fig. 2 Identification of a minimal methyltransferase sequence.

a, Schematic for the identification of a minimal sequence, truncated RNA from the 59nt RNA. b, Level of radioactivity incorporation for truncated RNAs after reaction with [methyl-3H] SAM, RNAs were incubated at 45 °C for 2 hours and assayed by centrifugal dialysis. Error bars are the standard deviation from the mean of 3 independent experiments, data points are shown.

Source data

Extended Data Fig. 3 Differential Scanning Calorimetry of SMRZ-1.

a, Differential scanning calorimetry curve for SMRZ-1 in 20 mM Tris–HCl, 20 mM KCl, 1 mM MgCl2, 0.1 mM CuSO4 buffer, pH 7.4 at total strand concentrations with 88.7 μM SMRZ-1 RNA. The calculated Tm and ΔH are indicated in the box. b, The structures of the methyl donor SAM, SAH, and the protein methyltransferase inhibitor Sinefungin SFG.

Extended Data Fig. 4 The crystal structure of SMRZ-1 RNA/U1A protein complex.

a, Primary sequence of the SMRZ-1-U1Abd RNA. The U1A linker region of the RNA is coloured in cyan. b, Cartoon presentation showing the U1A proteins and the SMRZ-1-U1Abd RNA molecules packed in the asymmetric unit of the crystal. U1A proteins are coloured in green, cyan, magenta, and yellow. RNA molecules are coloured in wheat and grey. c-d, Structural superposition of the two SMRZ-1-U1Abd RNA molecules.

Extended Data Fig. 5 The activity of the ribozyme with the U1A binding domain embedded.

Embedding the U1A binding domain did not affect ribozyme activity, nor did the inclusion of U1A protein in the reaction. Error bars are the standard deviation from the mean of 3 independent experiments, data points are shown. Error bars are the standard deviations of 3 independent experiments (shown as contrasting dots).

Source data

Extended Data Fig. 6 Structure of SMRZ-1-U1A RNA.

a, The 2Fo-Fc electron density maps of the SMRZ-1-U1Abd RNA. The maps are contoured at 1.2 level. The 5'- and 3'-ends of SMRZ-1 are shown as sticks in magenta and yellow, respectively. The U1A linker is coloured in green. b, The detailed sequence and secondary structure of SMRZ-1-U1Abd RNA. c, The detailed conformations of the nucleotides near the active site of SMRZ-1. Inset, the U6:G40 wobble base pair. For clarity, the stacking interactions between the nucleobases of U9, A35, A10, and C34 are omitted.

Extended Data Fig. 7 Mutational analysis of the methyltransferase ribozyme.

a, Secondary structure of the minimal SMRZ-1 (WT) sequence. The stacked planar pseudo triples are indicated by the grey shading. b, Normalised activity (relative to SMRZ-1) for point mutated RNAs after reaction with [methyl-3H] SAM. c, Further mutational analysis of SMRZ-1 to the A7 and the pseudo-triple nucleotides A10 and A24 (equivalent to the A35 position in the crystal structure RNA), normalised to SMRZ-1. For panels b and c error bars are the standard deviation from the mean of 3 independent experiments, data points are shown as dots.

Source data

Extended Data Fig. 8 Structure of SAM-complexed SMRZ-1-U1A RNA.

a, Overall structure of SMRZ-1-U1A RNA/U1A in the presence of SAM and Cu2+. The 5'- and 3'-ends of SMRZ-1 are coloured in magenta and yellow, respectively. The U1A linker is coloured in green. b-c, The 2Fo-Fc electron density maps of the SMRZ-1-U1A RNA and SAM and Cu2+, respectively. The maps are contoured at 1.0 level. d, Structural superposition of the SMRZ-1-U1A RNA molecules, which is coloured in white in the absence of SAM. Upon binding of SAM, the RNA is coloured as in a. Cu2+ is shown as black sphere in c. The SAM molecules are shown as red spheres in a and d, but as sticks in atomic colours (C, green; N, blue; O, red; S, orange) in c.

Extended Data Fig. 9 Distribution of candidate methyltransferase ribozyme sequences.

a, Table of natural SMRZ-1 ribozyme candidate sequences 16-40. The sequences are listed by classification and accession numbers. The alignment and activity relative to SMRZ-1 of each sequence and their relative position in the secondary structure in the RNA is shown. b, Methylation activity of sequences 16-40. The histograms show (Mauve, left axis) uncorrected incorporation of radioactivity (cpm) for each sample compared to the background measurement (Bkg) and the internal SMRZ-1 control for each experiment (separated by vertical dashed lines). The axis break from 300-1000 cpm shows the relatively low background signal (mean of 187 cpm ± 34 (n=15)), error bars are the standard deviations from the mean of 3 independent experiments (shown as contrasting dots). The right-hand (light blue) axis is the normalised (%) activity for each sequence relative to the SMRZ-1 control, for comparison between experiments, error bars are the standard deviations from the mean of 3 independent experiments (shown as contrasting dots).

Source data

Extended Data Fig. 10 The distribution of potential ribozyme sequences.

a, The numbers of candidate sequences classified by Kingdom, the number of unique sequences and the number of species harbouring candidate sequences. b, The numbers of candidate sequences identified in Bacteria and Archaea. Potential ribozyme sequences are classified by relative genome position, as sense or antisense strand, coding sequence (CDS), location within CDS (5’ or 3’), intergenic (between CDS) and sequences that have not been annotated. c, The numbers of candidate sequences present in Eukaryotes. Sequences are classified by relative genome position, as sense or antisense strand, exon or intron location, mix (exon and intron) or by annotation.

Supplementary Information

Supplementary Information

Supplementary Fig. 1 and Tables 1, 3 and 4.

Reporting Summary

Supplementary Table

Supplementary Tables 2, 5 and 6. Microsoft Excel file annotating sequences tabulated in Fig. 4c and Extended Data Fig. 9A.

Supplementary Data

Source Data Supplementary Figure 1

Source data

Source Data Fig. 1

Uncropped sequence gel.

Source Data Fig. 2

Source data Fig. 2

Source Data Fig. 4

Source data Fig. 4

Source Data Extended Data Fig. 1

Source data Extended data Fig 1

Source Data Extended Data Fig. 2

Source data Extended data Fig 2

Source Data Extended Data Fig. 5

Source data Extended data Fig 5

Source Data Extended Data Fig. 7

Source data Extended data Fig7

Source Data Extended Data Fig. 9

Source data Extended data Fig 9

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, H., Gao, Y., Zhang, L. et al. The identification and characterization of a selected SAM-dependent methyltransferase ribozyme that is present in natural sequences. Nat Catal 4, 872–881 (2021). https://doi.org/10.1038/s41929-021-00685-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41929-021-00685-z

This article is cited by

Search

Advanced search

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