1. Computational and Systems Biology
  2. Microbiology and Infectious Disease
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Operon mRNAs are organized into ORF-centric structures that predict translation efficiency

  1. David H Burkhardt
  2. Silvi Rouskin
  3. Yan Zhang
  4. Gene-Wei Li  Is a corresponding author
  5. Jonathan S Weissman  Is a corresponding author
  6. Carol A Gross  Is a corresponding author
  1. University of California, San Francisco, United States
  2. Howard Hughes Medical Institute, University of California, San Francisco, United States
  3. Massachusetts Institute of Technology, United States
Research Article
  • Cited 59
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Cite this article as: eLife 2017;6:e22037 doi: 10.7554/eLife.22037

Abstract

Bacterial mRNAs are organized into operons consisting of discrete open reading frames (ORFs) in a single polycistronic mRNA. Individual ORFs on the mRNA are differentially translated, with rates varying as much as 100-fold. The signals controlling differential translation are poorly understood. Our genome-wide mRNA secondary structure analysis indicated that operonic mRNAs are comprised of ORF-wide units of secondary structure that vary across ORF boundaries such that adjacent ORFs on the same mRNA molecule are structurally distinct. ORF translation rate is strongly correlated with its mRNA structure in vivo, and correlation persists, albeit in a reduced form, with its structure when translation is inhibited and with that of in vitro refolded mRNA. These data suggests that intrinsic ORF mRNA structure encodes a rough blueprint for translation efficiency. This structure is then amplified by translation, in a self-reinforcing loop, to provide the structure that ultimately specifies the translation of each ORF.

Article and author information

Author details

  1. David H Burkhardt

    Graduate Group in Biophysics, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Silvi Rouskin

    Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Yan Zhang

    Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5440-1414
  4. Gene-Wei Li

    Department of Biology, Massachusetts Institute of Technology, Cambridge, United States
    For correspondence
    gwli@mit.edu
    Competing interests
    The authors declare that no competing interests exist.
  5. Jonathan S Weissman

    Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
    For correspondence
    Jonathan.Weissman@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2445-670X
  6. Carol A Gross

    Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States
    For correspondence
    cgrossucsf@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5595-9732

Funding

Howard Hughes Medical Institute

  • Jonathan S Weissman

National Institutes of Health

  • David H Burkhardt
  • Yan Zhang
  • Carol A Gross

Helen Hay Whitney Foundation

  • Gene-Wei Li

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

Reviewing Editor

  1. Rachel Green, Johns Hopkins School of Medicine, United States

Publication history

  1. Received: October 3, 2016
  2. Accepted: January 27, 2017
  3. Accepted Manuscript published: January 31, 2017 (version 1)
  4. Version of Record published: February 20, 2017 (version 2)

Copyright

© 2017, Burkhardt 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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