Biology:Hfq protein

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Hfq protein with a bound sRNA.

The Hfq protein (also known as HF-I protein) encoded by the hfq gene was discovered in 1968 as an Escherichia coli host factor that was essential for replication of the bacteriophage Qβ.[1] It is now clear that Hfq is an abundant bacterial RNA binding protein which has many important physiological roles that are usually mediated by interacting with Hfq binding sRNA.

In E. coli, Hfq mutants show multiple stress response related phenotypes.[2] The Hfq protein is now known to regulate the translation of two major stress transcription factors ( σS (RpoS) and σE (RpoE) ) in Enterobacteria.[3][4][5] It also regulates sRNA in Vibrio cholerae, a specific example being MicX sRNA.[6] In Salmonella typhimurium, Hfq has been shown to be an essential virulence factor as its deletion attenuates the ability of S.typhimurium to invade epithelial cells, secrete virulence factors or survive in cultured macrophages.[7] In Salmonella, Hfq deletion mutants are also non motile and exhibit chronic activation of the sigma mediated envelope stress response.[8] A CLIP-Seq study of Hfq in Salmonella has revealed 640 binding sites across the Salmonella transcriptome. The majority of these binding sites was found in mRNAs and sRNAs.[9] In Photorhabdus luminescens, a deletion of the hfq gene causes loss of secondary metabolite production.[10]

Hfq mediates its pleiotropic effects through several mechanisms. It interacts with regulatory sRNA and facilitates their antisense interaction with their targets. It also acts independently to modulate mRNA decay (directing mRNA transcripts for degradation) and also acts as a repressor of mRNA translation. Genomic SELEX has been used to show that Hfq binding RNAs are enriched in the sequence motif 5'-AAYAAYAA-3'.[11] Hfq was also found to act on ribosome biogenesis in E. coli, specifically on the 30S subunit. Hfq mutants accumulate higher levels of immature small subunits and decreased translation accuracy.[12] This function on the bacterial ribosome could also account for the pleiotropic effect typical of Hfq deletion strains.[13]

Electron microscopy imaging reveals that, in addition to the expected localization of this protein in cytoplasmic regions and in the nucleoid, an important fraction of Hfq is located in close proximity to the membrane.[14]

Crystallographic structures

Six crystallographic structures of 4 different Hfq proteins have been published so far; E. coli Hfq (PDB: 1HK9​), P. aeruginosa Hfq in a low salt condition (1U1S​) and a high salt condition (1U1T​), Hfq from S. aureus with bound RNA (1KQ2​) and without (1KQ1​), and the Hfq(-like) protein from M. jannaschii (2QTX​).

All six structures confirm the hexameric ring-shape of a Hfq protein complex.

See also

References

  1. ↑ "Phage-specific and host proteins in the replication of bacteriophage RNA". Fed. Proc. 29 (3): 1170–5. 1970. PMID 4315363. 
  2. ↑ "Characterization of broadly pleiotropic phenotypes caused by an hfq insertion mutation in Escherichia coli K-12". Molecular Microbiology 13 (1): 35–49. July 1994. doi:10.1111/j.1365-2958.1994.tb00400.x. PMID 7984093. 
  3. ↑ "The RNA-binding protein HF-I, known as a host factor for phage Qbeta RNA replication, is essential for rpoS translation in Escherichia coli". Genes & Development 10 (9): 1143–51. May 1996. doi:10.1101/gad.10.9.1143. PMID 8654929. http://www.genesdev.org/cgi/pmidlookup?view=long&pmid=8654929. 
  4. ↑ "Hfq modulates the sigmaE-mediated envelope stress response and the sigma32-mediated cytoplasmic stress response in Escherichia coli". Journal of Bacteriology 189 (5): 1963–73. March 2007. doi:10.1128/JB.01243-06. PMID 17158661. 
  5. ↑ "Efficient translation of the RpoS sigma factor in Salmonella typhimurium requires host factor I, an RNA-binding protein encoded by the hfq gene". Journal of Bacteriology 178 (13): 3763–70. July 1996. doi:10.1128/jb.178.13.3763-3770.1996. PMID 8682778. 
  6. ↑ "RNase E-dependent processing stabilizes MicX, a Vibrio cholerae sRNA". Mol. Microbiol. 65 (2): 373–85. July 2007. doi:10.1111/j.1365-2958.2007.05796.x. PMID 17590231. 
  7. ↑ "The RNA chaperone Hfq is essential for the virulence of Salmonella typhimurium". Molecular Microbiology 63 (1): 193–217. January 2007. doi:10.1111/j.1365-2958.2006.05489.x. PMID 17163975. 
  8. ↑ "Loss of Hfq activates the sigmaE-dependent envelope stress response in Salmonella enterica". Molecular Microbiology 62 (3): 838–52. November 2006. doi:10.1111/j.1365-2958.2006.05413.x. PMID 16999834. 
  9. ↑ "Global RNA recognition patterns of post-transcriptional regulators Hfq and CsrA revealed by UV crosslinking in vivo". EMBO J 35 (9): 991–1011. 2016. doi:10.15252/embj.201593360. PMID 27044921. 
  10. ↑ "Photorhabdus-nematode symbiosis is dependent on hfq-mediated regulation of secondary metabolites". Environmental Microbiology 19 (1): 119–129. 2016. doi:10.1111/1462-2920.13502. PMID 27555343. 
  11. ↑ "Genomic SELEX for Hfq-binding RNAs identifies genomic aptamers predominantly in antisense transcripts.". Nucleic Acids Res 38 (11): 3794–808. 2010. doi:10.1093/nar/gkq032. PMID 20348540. 
  12. ↑ Andrade, José M.; Santos, Ricardo F. dos; Chelysheva, Irina; Ignatova, Zoya; Arraiano, Cecília M. (2018-04-16). "The RNA‐binding protein Hfq is important for ribosome biogenesis and affects translation fidelity" (in en). The EMBO Journal 37 (11): e97631. doi:10.15252/embj.201797631. ISSN 0261-4189. PMID 29669858. 
  13. ↑ Sharma, Indra Mani; Korman, Arthur; Woodson, Sarah A. (2018-05-15). "The Hfq chaperone helps the ribosome mature" (in en). The EMBO Journal 37 (11): e99616. doi:10.15252/embj.201899616. ISSN 0261-4189. PMID 29764978. 
  14. ↑ Mayer, Claudine, ed (2009). "Cellular electron microscopy imaging reveals the localization of the Hfq protein close to the bacterial membrane.". PLOS ONE 4 (12): e8301. doi:10.1371/journal.pone.0008301. PMID 20011543. Bibcode: 2009PLoSO...4.8301D.  
11. Mol Cell. 2002 Jan;9(1):23-30. Hfq: a bacterial Sm-like protein that mediates RNA-RNA interaction.Møller T1, Franch T,    Højrup P, Keene DR, Bächinger HP, Brennan RG, Valentin-Hansen P.
 
12. EMBO J. 2002 Jul 1;21(13):3546-56.Structures of the pleiotropic translational regulator Hfq and an Hfq-RNA complex: a bacterial Sm-like protein. Schumacher MA1, Pearson RF, Møller T, Valentin-Hansen P, Brennan RG.

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