1. Structural Biology and Molecular Biophysics
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Acidic C-terminal domains autoregulate the RNA chaperone Hfq

  1. Andrew Santiago-Frangos
  2. Jeliazko R Jeliazkov
  3. Jeffrey J Gray
  4. Sarah A Woodson  Is a corresponding author
  1. Johns Hopkins University, United States
Research Article
  • Cited 15
  • Views 1,599
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Cite this article as: eLife 2017;6:e27049 doi: 10.7554/eLife.27049

Abstract

The RNA chaperone Hfq is an Sm protein that facilitates base pairing between bacterial small RNAs (sRNAs) and mRNAs involved in stress response and pathogenesis. Hfq possesses an intrinsically disordered C-terminal domain (CTD) that may tune the function of the Sm domain in different organisms. In Escherichia coli, the Hfq CTD increases kinetic competition between sRNAs and recycles Hfq from the sRNA-mRNA duplex. Here, de novo Rosetta modeling and competitive binding experiments show that the acidic tip of the E. coli Hfq CTD transiently binds the basic Sm core residues necessary for RNA annealing. The CTD tip competes against non-specific RNA binding, facilitates dsRNA release, and prevents indiscriminate DNA aggregation, suggesting that this acidic peptide mimics nucleic acid to auto-regulate RNA binding to the Sm ring. The mechanism of CTD auto-inhibition predicts the chaperone function of Hfq in bacterial genera and illuminates how Sm proteins may evolve new functions.

Article and author information

Author details

  1. Andrew Santiago-Frangos

    Cell, Molecular and Developmental Biology and Biophysics Program, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9615-065X
  2. Jeliazko R Jeliazkov

    Program in Molecular Biophysics, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4249-1955
  3. Jeffrey J Gray

    Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6380-2324
  4. Sarah A Woodson

    T. C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, United States
    For correspondence
    swoodson@jhu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0170-1987

Funding

National Institute of General Medical Sciences (R01 GM120425-01)

  • Sarah A Woodson

National Institute of General Medical Sciences (R01 GM078221)

  • Jeffrey J Gray

National Institute of General Medical Sciences (T32 GM008403-25)

  • Jeliazko R Jeliazkov

National Institute of General Medical Sciences (T32 GM007231-40)

  • Andrew Santiago-Frangos

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

Reviewing Editor

  1. Ben F Luisi, University of Cambridge, United Kingdom

Publication history

  1. Received: March 22, 2017
  2. Accepted: August 3, 2017
  3. Accepted Manuscript published: August 9, 2017 (version 1)
  4. Version of Record published: September 20, 2017 (version 2)
  5. Version of Record updated: October 12, 2017 (version 3)

Copyright

© 2017, Santiago-Frangos 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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