Intermolecular base stacking mediates RNA-RNA interaction in a crystal structure of the RNA chaperone Hfq

TY - JOUR

T1 - Intermolecular base stacking mediates RNA-RNA interaction in a crystal structure of the RNA chaperone Hfq

AU - Schulz, Eike C

AU - Seiler, Markus

AU - Zuliani, Cecilia

AU - Voigt, Franka

AU - Rybin, Vladimir

AU - Pogenberg, Vivian

AU - Mücke, Norbert

AU - Wilmanns, Matthias

AU - Gibson, Toby J

AU - Barabas, Orsolya

PY - 2017/8/29

Y1 - 2017/8/29

N2 - The RNA-chaperone Hfq catalyses the annealing of bacterial small RNAs (sRNAs) with target mRNAs to regulate gene expression in response to environmental stimuli. Hfq acts on a diverse set of sRNA-mRNA pairs using a variety of different molecular mechanisms. Here, we present an unusual crystal structure showing two Hfq-RNA complexes interacting via their bound RNA molecules. The structure contains two Hfq6:A18 RNA assemblies positioned face-to-face, with the RNA molecules turned towards each other and connected via interdigitating base stacking interactions at the center. Biochemical data further confirm the observed interaction, and indicate that RNA-mediated contacts occur between Hfq-RNA complexes with various (ARN)X motif containing RNA sequences in vitro, including the stress response regulator OxyS and its target, fhlA. A systematic computational survey also shows that phylogenetically conserved (ARN)X motifs are present in a subset of sRNAs, some of which share similar modular architectures. We hypothesise that Hfq can co-opt RNA-RNA base stacking, an unanticipated structural trick, to promote the interaction of (ARN)X motif containing sRNAs with target mRNAs on a "speed-dating" fashion, thereby supporting their regulatory function.

AB - The RNA-chaperone Hfq catalyses the annealing of bacterial small RNAs (sRNAs) with target mRNAs to regulate gene expression in response to environmental stimuli. Hfq acts on a diverse set of sRNA-mRNA pairs using a variety of different molecular mechanisms. Here, we present an unusual crystal structure showing two Hfq-RNA complexes interacting via their bound RNA molecules. The structure contains two Hfq6:A18 RNA assemblies positioned face-to-face, with the RNA molecules turned towards each other and connected via interdigitating base stacking interactions at the center. Biochemical data further confirm the observed interaction, and indicate that RNA-mediated contacts occur between Hfq-RNA complexes with various (ARN)X motif containing RNA sequences in vitro, including the stress response regulator OxyS and its target, fhlA. A systematic computational survey also shows that phylogenetically conserved (ARN)X motifs are present in a subset of sRNAs, some of which share similar modular architectures. We hypothesise that Hfq can co-opt RNA-RNA base stacking, an unanticipated structural trick, to promote the interaction of (ARN)X motif containing sRNAs with target mRNAs on a "speed-dating" fashion, thereby supporting their regulatory function.

KW - Amino Acid Motifs

KW - Base Sequence

KW - Binding Sites

KW - Escherichia coli Proteins/chemistry

KW - Host Factor 1 Protein/chemistry

KW - Models, Molecular

KW - Molecular Structure

KW - Nucleic Acid Conformation

KW - Protein Binding

KW - RNA/chemistry

KW - RNA, Messenger/chemistry

KW - Solutions/chemistry

KW - Structure-Activity Relationship

U2 - 10.1038/s41598-017-10085-8

DO - 10.1038/s41598-017-10085-8

M3 - SCORING: Journal article

C2 - 28852099

VL - 7

SP - 9903

JO - SCI REP-UK

JF - SCI REP-UK

SN - 2045-2322

IS - 1

ER -