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Structural analysis of human 2′-O-ribose methyltransferases involved in mRNA cap structure formation

Author

Listed:
  • Miroslaw Smietanski

    (Laboratory of Bioinformatics and Protein Engineering, International Institute of Molecular and Cell Biology in Warsaw
    Laboratory of Protein Structure, International Institute of Molecular and Cell Biology in Warsaw)

  • Maria Werner

    (Laboratory of Bioinformatics and Protein Engineering, International Institute of Molecular and Cell Biology in Warsaw)

  • Elzbieta Purta

    (Laboratory of Bioinformatics and Protein Engineering, International Institute of Molecular and Cell Biology in Warsaw)

  • Katarzyna H. Kaminska

    (Laboratory of Bioinformatics and Protein Engineering, International Institute of Molecular and Cell Biology in Warsaw)

  • Janusz Stepinski

    (Institute of Experimental Physics, Faculty of Physics, University of Warsaw)

  • Edward Darzynkiewicz

    (Institute of Experimental Physics, Faculty of Physics, University of Warsaw
    Centre of New Technologies, University of Warsaw)

  • Marcin Nowotny

    (Laboratory of Protein Structure, International Institute of Molecular and Cell Biology in Warsaw)

  • Janusz M. Bujnicki

    (Laboratory of Bioinformatics and Protein Engineering, International Institute of Molecular and Cell Biology in Warsaw
    Laboratory of Bioinformatics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University)

Abstract

The 5′ cap of human messenger RNA contains 2′-O-methylation of the first and often second transcribed nucleotide that is important for its processing, translation and stability. Human enzymes that methylate these nucleotides, termed CMTr1 and CMTr2, respectively, have recently been identified. However, the structures of these enzymes and their mechanisms of action remain unknown. In the present study, we solve the crystal structures of the active CMTr1 catalytic domain in complex with a methyl group donor and a capped oligoribonucleotide, thereby revealing the mechanism of specific recognition of capped RNA. This mechanism differs significantly from viral enzymes, thus providing a framework for their specific targeting. Based on the crystal structure of CMTr1, a comparative model of the CMTr2 catalytic domain is generated. This model, together with mutational analysis, leads to the identification of residues involved in RNA and methyl group donor binding.

Suggested Citation

  • Miroslaw Smietanski & Maria Werner & Elzbieta Purta & Katarzyna H. Kaminska & Janusz Stepinski & Edward Darzynkiewicz & Marcin Nowotny & Janusz M. Bujnicki, 2014. "Structural analysis of human 2′-O-ribose methyltransferases involved in mRNA cap structure formation," Nature Communications, Nature, vol. 5(1), pages 1-10, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4004
    DOI: 10.1038/ncomms4004
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