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.
Highlights
Host factor for RNA phage Qb replication (Hfq) is found in most sequenced bacterial genomes (Sun et al, 2002) and plays a well characterized role in post-transcriptional regulation by small noncoding RNA (Gottesman et al, 2006; Storz et al, 2011)
We propose that the acidic C-terminal domain (CTD) tip transiently binds the rim of E. coli Hfq and makes distributed interactions with basic residues, thereby modulating RNA and DNA binding and RNA annealing
The start of the CTD region is delineated by a proline at position 64 of E. coli Hfq that is strongly conserved across all clades
Summary
Host factor for RNA phage Qb replication (Hfq) is found in most sequenced bacterial genomes (Sun et al, 2002) and plays a well characterized role in post-transcriptional regulation by small noncoding RNA (sRNA) (Gottesman et al, 2006; Storz et al, 2011). In E. coli and many Gram negative bacteria, the distal face of Hfq binds to AAN triplet repeats (Mikulecky et al, 2004; Link et al, 2009) found in mRNA leaders (Link et al, 2009; Soper et al, 2011) and certain sRNAs (Schu et al, 2015; Małecka et al, 2015) In addition to these sequence-specific RNA binding sites, arginine-rich basic patches at the rim of the E. coli Hfq hexamer interact with the sRNA body (Zhang et al, 2002; Otaka et al, 2011; Sauer et al, 2012; Ishikawa et al, 2012; Zhang et al, 2013) and facilitate annealing with target mRNAs (Panja et al, 2013; Zheng et al, 2016)
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