Acidic C-terminal domains autoregulate the RNA chaperone Hfq

Andrew Santiago-Frangos, Jeliazko R. Jeliazkov, Jeffrey J. Gray, Sarah A. Woodson

Research output: Contribution to journalArticle

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 nonspecific 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.

LanguageEnglish (US)
Article numbere27049
JournaleLife
Volume6
DOIs
StatePublished - Aug 9 2017

Fingerprint

RNA
Escherichia coli
Bacterial RNA
Peptide Nucleic Acids
Messenger RNA
Competitive Binding
Base Pairing
Proteins
Agglomeration
Annealing
DNA
Kinetics
Experiments

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Santiago-Frangos, A., Jeliazkov, J. R., Gray, J. J., & Woodson, S. A. (2017). Acidic C-terminal domains autoregulate the RNA chaperone Hfq. eLife, 6, [e27049]. DOI: 10.7554/eLife.27049

Acidic C-terminal domains autoregulate the RNA chaperone Hfq. / Santiago-Frangos, Andrew; Jeliazkov, Jeliazko R.; Gray, Jeffrey J.; Woodson, Sarah A.

In: eLife, Vol. 6, e27049, 09.08.2017.

Research output: Contribution to journalArticle

Santiago-Frangos, A, Jeliazkov, JR, Gray, JJ & Woodson, SA 2017, 'Acidic C-terminal domains autoregulate the RNA chaperone Hfq' eLife, vol 6, e27049. DOI: 10.7554/eLife.27049
Santiago-Frangos A, Jeliazkov JR, Gray JJ, Woodson SA. Acidic C-terminal domains autoregulate the RNA chaperone Hfq. eLife. 2017 Aug 9;6. e27049. Available from, DOI: 10.7554/eLife.27049
Santiago-Frangos, Andrew ; Jeliazkov, Jeliazko R. ; Gray, Jeffrey J. ; Woodson, Sarah A./ Acidic C-terminal domains autoregulate the RNA chaperone Hfq. In: eLife. 2017 ; Vol. 6.
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