1. Computational and Systems Biology
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Kinetic modeling predicts a stimulatory role for ribosome collisions at elongation stall sites in bacteria

  1. Michael A Ferrin
  2. Arvind R Subramaniam  Is a corresponding author
  1. Fred Hutchinson Cancer Research Center, United States
Research Article
  • Cited 8
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Cite this article as: eLife 2017;6:e23629 doi: 10.7554/eLife.23629

Abstract

Ribosome stalling on mRNAs can decrease protein expression. To decipher ribosome kinetics at stall sites, we induced ribosome stalling at specific codons by starving the bacterium Escherichia coli for the cognate amino acid. We measured protein synthesis rates from a reporter library of over 100 variants that encoded systematic perturbations of translation initiation rate, the number of stall sites, and the distance between stall sites. Our measurements are quantitatively inconsistent with two widely-used kinetic models for stalled ribosomes: ribosome traffic jams that block initiation, and abortive (premature) termination of stalled ribosomes. Rather, our measurements support a model in which collision with a trailing ribosome causes abortive termination of the stalled ribosome. In our computational analysis, ribosome collisions selectively stimulate abortive termination without fine-tuning of kinetic rate parameters at ribosome stall sites. We propose that ribosome collisions serve as a robust timer for translational quality control pathways to recognize stalled ribosomes.

Article and author information

Author details

  1. Michael A Ferrin

    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Arvind R Subramaniam

    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States
    For correspondence
    rasi@fredhutch.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6145-4303

Funding

National Institute of General Medical Sciences (R35 GM119835,R00 GM107113)

  • Michael A Ferrin
  • Arvind R Subramaniam

Fred Hutchinson Cancer Research Center

  • Michael A Ferrin
  • Arvind R Subramaniam

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

Reviewing Editor

  1. Alan G Hinnebusch, National Institutes of Health, United States

Publication history

  1. Received: November 26, 2016
  2. Accepted: May 10, 2017
  3. Accepted Manuscript published: May 12, 2017 (version 1)
  4. Version of Record published: May 26, 2017 (version 2)

Copyright

© 2017, Ferrin & Subramaniam

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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