1. Biochemistry and Chemical Biology
  2. Structural Biology and Molecular Biophysics
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Structure and mechanistic features of the prokaryotic minimal RNase P

  1. Rebecca Feyh
  2. Nadine Bianca Waeber
  3. Simone Prinz
  4. Pietro Ivan Giammarinaro
  5. Gert Bange
  6. Georg Hochberg
  7. Roland Karl Hartmann  Is a corresponding author
  8. Florian Altegoer  Is a corresponding author
  1. Institute of Pharmaceutical Chemistry, Philipps-University Marburg,, Germany
  2. Department of Structural Biology, Max Planck Institute of Biophysics, Germany
  3. Center for Synthetic Microbiology and Department of Chemistry, Philipps-University Marburg, Germany
  4. Max Planck Institute of Biophysics, Germany
  5. Philipps-Universitaet Marburg, Germany
Research Article
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Cite this article as: eLife 2021;10:e70160 doi: 10.7554/eLife.70160

Abstract

Endonucleolytic removal of 5'-leader sequences from tRNA precursor transcripts (pre-tRNAs) by RNase P is essential for protein synthesis. Beyond RNA-based RNase P enzymes, protein-only versions of the enzyme exert this function in various Eukarya (there termed PRORPs) and in some bacteria (Aquifex aeolicus and close relatives); both enzyme types belong to distinct subgroups of the PIN domain metallonuclease superfamily. Homologs of Aquifex RNase P (HARPs) are also expressed in some other bacteria and many archaea, where they coexist with RNA-based RNase P and do not represent the main RNase P activity. Here we solved the structure of the bacterial HARP from Halorhodospira halophila by cryo-EM revealing a novel screw-like dodecameric assembly. Biochemical experiments demonstrate that oligomerization is required for RNase P activity of HARPs. We propose that the tRNA substrate binds to an extended spike-helix (SH) domain that protrudes from the screw-like assembly to position the 5'-end in close proximity to the active site of the neighboring dimer. The structure suggests that eukaryotic PRORPs and prokaryotic HARPs recognize the same structural elements of pre-tRNAs (tRNA elbow region and cleavage site). Our analysis thus delivers the structural and mechanistic basis for pre-tRNA processing by the prokaryotic HARP system.

Data availability

Coordinates and structure factors have been deposited within the protein data bank (PDB) and the electron microscopy data bank (EMDB) under accession codes: 7OG5 and EMD-12878. The authors declare that all other data supporting the findings of this study are available within the article and its supplementary information files.

Article and author information

Author details

  1. Rebecca Feyh

    Institute of Pharmaceutical Chemistry, Philipps-University Marburg,, Marburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Nadine Bianca Waeber

    Institute of Pharmaceutical Chemistry, Philipps-University Marburg,, Marburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Simone Prinz

    Department of Structural Biology, Max Planck Institute of Biophysics, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Pietro Ivan Giammarinaro

    Chemistry, Center for Synthetic Microbiology and Department of Chemistry, Philipps-University Marburg, Marburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0356-8481
  5. Gert Bange

    Max Planck Institute of Biophysics, Marburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Georg Hochberg

    Max Planck Institute of Biophysics, Marburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Roland Karl Hartmann

    Philipps-Universitaet Marburg, Marburg, Germany
    For correspondence
    roland.hartmann@staff.uni-marburg.de
    Competing interests
    The authors declare that no competing interests exist.
  8. Florian Altegoer

    Chemistry, Center for Synthetic Microbiology and Department of Chemistry, Philipps-University Marburg, Marburg, Germany
    For correspondence
    altegoer@uni-marburg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6012-9047

Funding

Deutsche Forschungsgemeinschaft (HA 1672/19-1)

  • Roland Karl Hartmann

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Philip A Cole, Harvard Medical School, United States

Publication history

  1. Received: May 7, 2021
  2. Accepted: June 25, 2021
  3. Accepted Manuscript published: June 28, 2021 (version 1)
  4. Version of Record published: July 8, 2021 (version 2)

Copyright

© 2021, Feyh et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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