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.
- Sarah A Woodson
- Jeffrey J Gray
- Jeliazko R Jeliazkov
- Andrew Santiago-Frangos
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Ben F Luisi, Reviewing Editor, University of Cambridge, United Kingdom
- Received: March 22, 2017
- Accepted: August 3, 2017
- Accepted Manuscript published: August 9, 2017 (version 1)
© 2017, Santiago-Frangos et al.
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