Mapping Hfq-RNA interaction surfaces using tryptophan fluorescence quenching

Nucleic Acids Res. 2014 Feb;42(4):2736-49. doi: 10.1093/nar/gkt1171. Epub 2013 Nov 27.

Abstract

Hfq is a posttranscriptional riboregulator and RNA chaperone that binds small RNAs and target mRNAs to effect their annealing and message-specific regulation in response to environmental stressors. Structures of Hfq-RNA complexes indicate that U-rich sequences prefer the proximal face and A-rich sequences the distal face; however, the Hfq-binding sites of most RNAs are unknown. Here, we present an Hfq-RNA mapping approach that uses single tryptophan-substituted Hfq proteins, all of which retain the wild-type Hfq structure, and tryptophan fluorescence quenching (TFQ) by proximal RNA binding. TFQ properly identified the respective distal and proximal binding of A15 and U6 RNA to Gram-negative Escherichia coli (Ec) Hfq and the distal face binding of (AA)3A, (AU)3A and (AC)3A to Gram-positive Staphylococcus aureus (Sa) Hfq. The inability of (GU)3G to bind the distal face of Sa Hfq reveals the (R-L)n binding motif is a more restrictive (A-L)n binding motif. Remarkably Hfq from Gram-positive Listeria monocytogenes (Lm) binds (GU)3G on its proximal face. TFQ experiments also revealed the Ec Hfq (A-R-N)n distal face-binding motif should be redefined as an (A-A-N)n binding motif. TFQ data also demonstrated that the 5'-untranslated region of hfq mRNA binds both the proximal and distal faces of Ec Hfq and the unstructured C-terminus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 5' Untranslated Regions
  • Amino Acid Motifs
  • Binding Sites
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Fluorescence
  • Host Factor 1 Protein / chemistry*
  • Host Factor 1 Protein / genetics
  • Host Factor 1 Protein / metabolism
  • Listeria monocytogenes
  • Models, Molecular
  • Mutation
  • Protein Binding
  • RNA / chemistry
  • RNA / metabolism*
  • Staphylococcus aureus
  • Tryptophan / chemistry*

Substances

  • 5' Untranslated Regions
  • Escherichia coli Proteins
  • Hfq protein, E coli
  • Host Factor 1 Protein
  • RNA
  • Tryptophan

Associated data

  • PDB/4JLI
  • PDB/4JRI
  • PDB/4JRK
  • PDB/4JUV
  • PDB/F11W
  • PDB/F39W
  • PDB/F42W
  • PDB/Y25W