Architectural principles for Hfq/Crc-mediated regulation of gene expression

  1. Xue Yuan Pei
  2. Tom Dendooven
  3. Elisabeth Sonnleitner
  4. Shaoxia Chen
  5. Udo Blasi  Is a corresponding author
  6. Ben F Luisi  Is a corresponding author
  1. University of Cambridge, United Kingdom
  2. University of Vienna, Austria
  3. MRC Laboratory of Molecular Biology, United Kingdom

Abstract

In diverse bacterial species, the global regulator Hfq contributes to post-transcriptional networks that control expression of numerous genes. Hfq of the opportunistic pathogen Pseudomonas aeruginosa inhibits translation of target transcripts by forming a regulatory complex with the catabolite repression protein Crc. This repressive complex acts part of an intricate mechanism of preferred nutrient utilisation. We describe high-resolution cryo-EM structures of the assembly of Hfq and Crc bound to the translation initiation site of a target mRNA. The core of the assembly is formed through interactions of two cognate RNAs, two Hfq hexamers and a Crc pair. Additional Crc protomers are recruited to the core to generate higher-order assemblies with demonstrated regulatory activity in vivo. This study reveals how Hfq cooperates with a partner protein to regulate translation, and provides a structural basis for an RNA code that guides global regulators to interact cooperatively and regulate different RNA targets.

Data availability

CryoEM data have been deposited

The following data sets were generated

Article and author information

Author details

  1. Xue Yuan Pei

    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Tom Dendooven

    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Elisabeth Sonnleitner

    Department of Microbiology, Immunobiology and Genetics, University of Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  4. Shaoxia Chen

    MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Udo Blasi

    Department of Microbiology, Immunobiology and Genetics, University of Vienna, Vienna, Austria
    For correspondence
    udo.blaesi@univie.ac.at
    Competing interests
    The authors declare that no competing interests exist.
  6. Ben F Luisi

    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    bfl20@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1144-9877

Funding

Wellcome Trust (200873/Z/16/Z)

  • Ben F Luisi

Austrian Science Fund (P28711-B22)

  • Udo Blasi

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

Reviewing Editor

  1. Anna Marie Pyle, Yale University, United States

Version history

  1. Received: October 26, 2018
  2. Accepted: February 11, 2019
  3. Accepted Manuscript published: February 13, 2019 (version 1)
  4. Version of Record published: March 18, 2019 (version 2)

Copyright

© 2019, Pei 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. Xue Yuan Pei
  2. Tom Dendooven
  3. Elisabeth Sonnleitner
  4. Shaoxia Chen
  5. Udo Blasi
  6. Ben F Luisi
(2019)
Architectural principles for Hfq/Crc-mediated regulation of gene expression
eLife 8:e43158.
https://doi.org/10.7554/eLife.43158

Share this article

https://doi.org/10.7554/eLife.43158

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