Structural characterization of NrnC identifies unifying features of dinucleotidases

  1. Justin D Lormand
  2. Soo-Kyoung Kim
  3. George A Walters-Marrah
  4. Bryce A Brownfield
  5. J Christopher Fromme
  6. Wade C Winkler
  7. Jonathan R Goodson
  8. Vincent T Lee
  9. Holger Sondermann  Is a corresponding author
  1. Cornell University, United States
  2. University of Maryland, United States
  3. Centre for Structural Systems Biology (CSSB), Germany

Abstract

RNA degradation is fundamental for cellular homeostasis. The process is carried out by various classes of endolytic and exolytic enzymes that together degrade an RNA polymer to mono-ribonucleotides. Within the exoribonucleases, nano-RNases play a unique role as they act on the smallest breakdown products and hence catalyze the final steps in the process. We recently showed that oligoribonuclease (Orn) acts as a dedicated diribonucleotidase, defining the ultimate step in RNA degradation that is crucial for cellular fitness (Kim et al., 2019). Whether such a specific activity exists in organisms that lack Orn-type exoribonucleases remained unclear. Through quantitative structure-function analyses we show here that NrnC-type RNases share this narrow substrate length preference with Orn. Although NrnC employs similar structural features that distinguish these two classes as dinucleotidases from other exonucleases, the key determinants for dinucleotidase activity are realized through distinct structural scaffolds. The structures together with comparative genomic analyses of the phylogeny of DEDD-type exoribonucleases indicates convergent evolution as the mechanism of how dinucleotidase activity emerged repeatedly in various organisms. The evolutionary pressure to maintain dinucleotidase activity further underlines the important role these analogous proteins play for cell growth.

Data availability

The atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.rcsb.org (PDB ID codes 7MPL, 7MPM, 7MPN, 7MPO, 7MPP, 7MPQ, 7MPR, 7MPS, 7MPT, 7MPU, 7MQB/EMD-23941, 7MQD/EMD-23943, 7MQF/EMD-23945, 7MQH/EMD-23947, 7MQC/EMD-23942, 7MQE/EMD-23944, 7MQG/EMD-23946, 7MQI/EMD-23948).

Article and author information

Author details

  1. Justin D Lormand

    Department of Molecular Medicine, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7803-4716
  2. Soo-Kyoung Kim

    Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. George A Walters-Marrah

    Department of Molecular Medicine, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Bryce A Brownfield

    Department of Molecular Medicine, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. J Christopher Fromme

    Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8837-0473
  6. Wade C Winkler

    Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Jonathan R Goodson

    Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Vincent T Lee

    Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3593-0318
  9. Holger Sondermann

    Deutsches Elektronen-Synchrotron DESY, Centre for Structural Systems Biology (CSSB), Hamburg, Germany
    For correspondence
    holger.sondermann@cssb-hamburg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2211-6234

Funding

National Institutes of Health (R01AI142400)

  • Vincent T Lee

National Institutes of Health (R01GM123609)

  • Holger Sondermann

National Institutes of Health (R35GM136258)

  • J Christopher Fromme

The funding sources were not involved in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Bryce E Nickels, Rutgers University, United States

Publication history

  1. Received: May 12, 2021
  2. Accepted: September 8, 2021
  3. Accepted Manuscript published: September 17, 2021 (version 1)
  4. Version of Record published: October 5, 2021 (version 2)
  5. Version of Record updated: January 28, 2022 (version 3)

Copyright

© 2021, Lormand 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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  1. Justin D Lormand
  2. Soo-Kyoung Kim
  3. George A Walters-Marrah
  4. Bryce A Brownfield
  5. J Christopher Fromme
  6. Wade C Winkler
  7. Jonathan R Goodson
  8. Vincent T Lee
  9. Holger Sondermann
(2021)
Structural characterization of NrnC identifies unifying features of dinucleotidases
eLife 10:e70146.
https://doi.org/10.7554/eLife.70146

Further reading

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