Architectural principles for Hfq/Crc-mediated regulation of gene expression

Elife. 2019 Feb 13;8:e43158. doi: 10.7554/eLife.43158.


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.

Keywords: Pseudomonas aeruginosa; metabolic regulation; molecular biophysics; riboregulation; structural biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / ultrastructure
  • Catabolite Repression / genetics
  • Cryoelectron Microscopy
  • Gene Expression Regulation, Bacterial / genetics
  • Host Factor 1 Protein / chemistry*
  • Host Factor 1 Protein / genetics
  • Host Factor 1 Protein / ultrastructure
  • Multiprotein Complexes / chemistry*
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / ultrastructure
  • Peptide Chain Initiation, Translational / genetics
  • Promoter Regions, Genetic / genetics
  • Protein Conformation
  • Pseudomonas aeruginosa / chemistry*
  • Pseudomonas aeruginosa / genetics
  • RNA, Bacterial / genetics
  • RNA, Messenger / genetics
  • Repressor Proteins / chemistry*
  • Repressor Proteins / genetics
  • Repressor Proteins / ultrastructure


  • Bacterial Proteins
  • Host Factor 1 Protein
  • Multiprotein Complexes
  • RNA, Bacterial
  • RNA, Messenger
  • Repressor Proteins
  • crc protein, Pseudomonas