Architectural principles for Hfq/Crc-mediated regulation of gene expression
Xue Yuan Pei,
Tom Dendooven,
Elisabeth Sonnleitner,
Shaoxia Chen,
Udo Bläsi,
Ben F Luisi
Affiliations
Xue Yuan Pei
Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
Tom Dendooven
Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
Elisabeth Sonnleitner
Department of Microbiology, Immunobiology and Genetics, Max F Perutz Laboratories, Center of Molecular Biology, University of Vienna, Vienna Biocenter, Vienna, Austria
Shaoxia Chen
MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
Udo Bläsi
Department of Microbiology, Immunobiology and Genetics, Max F Perutz Laboratories, Center of Molecular Biology, University of Vienna, Vienna Biocenter, Vienna, Austria
In diverse bacterial species, the global regulator Hfq contributes to post-transcriptional networks that control expression of numerous genes. Hfq of the opportunistic pathogen Pseudomonas aeruginosa inhibits translation of target transcripts by forming a regulatory complex with the catabolite repression protein Crc. This repressive complex acts as part of an intricate mechanism of preferred nutrient utilisation. We describe high-resolution cryo-EM structures of the assembly of Hfq and Crc bound to the translation initiation site of a target mRNA. The core of the assembly is formed through interactions of two cognate RNAs, two Hfq hexamers and a Crc pair. Additional Crc protomers are recruited to the core to generate higher-order assemblies with demonstrated regulatory activity in vivo. This study reveals how Hfq cooperates with a partner protein to regulate translation, and provides a structural basis for an RNA code that guides global regulators to interact cooperatively and regulate different RNA targets.
