A bacterial riboswitch class for the thiamin precursor HMP-PP employs a terminator-embedded aptamer

Abstract

We recently implemented a bioinformatics pipeline that can uncover novel, but rare, riboswitch candidates as well as other noncoding RNA structures in bacteria. A prominent candidate revealed by our initial search efforts was called the 'thiS motif' because of its frequent association with a gene coding for the ThiS protein, which delivers sulfur to form the thiazole moiety of the thiamin precursor HET-P. In the current report, we describe biochemical and genetic data demonstrating that thiS motif RNAs function as sensors of the thiamin precursor HMP-PP, which is fused with HET-P ultimately to form the final active coenzyme thiamin pyrophosphate (TPP). HMP-PP riboswitches exhibit a distinctive architecture wherein an unusually small ligand-sensing aptamer is almost entirely embedded within an otherwise classic intrinsic transcription terminator stem. This arrangement yields remarkably compact genetic switches that bacteria use to tune the levels of thiamin precursors during the biosynthesis of this universally distributed coenzyme.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Ruben M Atilho

    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Gayan Mirihana Arachchilage

    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Etienne B Greenlee

    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Kirsten M Knecht

    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Ronald R Breaker

    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, United States
    For correspondence
    ronald.breaker@yale.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2165-536X

Funding

National Institutes of Health (P01 GM022778)

  • Ronald R Breaker

National Science Foundation (Graduate Student Fellowship)

  • Ruben M Atilho

Howard Hughes Medical Institute (Investigator Funding)

  • Ronald R Breaker

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

Reviewing Editor

  1. Ailong Ke, Cornell University

Publication history

  1. Received: January 15, 2019
  2. Accepted: April 4, 2019
  3. Accepted Manuscript published: April 5, 2019 (version 1)
  4. Version of Record published: April 23, 2019 (version 2)

Copyright

© 2019, Atilho 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. Ruben M Atilho
  2. Gayan Mirihana Arachchilage
  3. Etienne B Greenlee
  4. Kirsten M Knecht
  5. Ronald R Breaker
(2019)
A bacterial riboswitch class for the thiamin precursor HMP-PP employs a terminator-embedded aptamer
eLife 8:e45210.
https://doi.org/10.7554/eLife.45210

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