MicroReview: The bacterial Sm‐like protein Hfq: a key player in RNA transactions

Valentin‐Hansen, Poul; Eriksen, Maiken; Udesen, Christina

doi:10.1111/j.1365-2958.2003.03935.x

Cited by 458 publications

(395 citation statements)

References 55 publications

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“…The cyanobacterial Hfq protein is considerably shorter than the E. coli Hfq protein and lacks some of the signature residues for the Sm-1 and Sm-2 motifs (Fig. 1A) (47). To investigate the function of the predicted Hfq orthologue from Anabaena sp.…”

Section: Resultsmentioning

confidence: 99%

“…The Hfq protein, initially identified as a host factor required for Q␤ bacteriophage replication (17), acts as a global posttranscriptional regulator in enterobacteria (34,47). In Escherichia coli, Hfq has been shown to regulate gene expression by binding to small RNAs (sRNAs).…”

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confidence: 99%

“…Subsequently, a BLAST search using the Anabaena Hfq sequence as a query identified Hfq homologues in a wide variety of unicellular and filamentous cyanobacteria, including Synechocystis sp. strain PCC 6803 and Prochlorococcus (47). The cyanobacterial Hfqs constitute a new group of Hfq proteins, with differences in some of the highly conserved residues present in the Sm-1 motif of the enterobacterial Hfq as well as the signature sequence in the Sm-2 region (4, 47) (Fig.…”

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confidence: 99%

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Hfq Is Required for Optimal Nitrate Assimilation in the Cyanobacterium Anabaena sp. Strain PCC 7120

Puerta-Fernández

Vioque

2011

Journal of Bacteriology

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Hfq is an RNA binding protein involved in posttranscriptional regulation of gene expression in bacteria. It acts by binding to regulatory small RNAs (sRNAs), which confer specificity for the regulation. Recently, orthologues of the Hfq protein were annotated in cyanobacterial genomes, although its capacity to regulate gene expression by interacting with sRNAs has not been yet demonstrated. Anabaena sp. strain PCC 7120 is a filamentous cyanobacterium that, in the absence of combined nitrogen, is able to fix atmospheric nitrogen by differentiating specialized cells called heterocysts. We have generated an hfq knockout mutant of Anabaena sp. PCC 7120. Deletion of this gene results in differentiation of heterocysts in the presence of nitrate, suggesting a defect in nitrate assimilation. We show that hfq mutant cells are affected in transport and use of nitrate and nitrite. An analysis of the expression of several genes in the nir operon, encoding different elements of the nitrate assimilation pathway, demonstrates a downregulation of their transcription in mutant cells. We also observed that genes ntcB and cnaT, involved in the regulation of the nir operon, show a lower expression in cells lacking Hfq. Finally, when hfq was reintroduced in the mutant, heterocyst differentiation was no longer observed in the presence of nitrate. Therefore, our results indicate that the RNA chaperone Hfq is involved in the regulation of the nir operon, although the mechanism for this regulation is still unknown.

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Section: Resultsmentioning

confidence: 99%

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Hfq Is Required for Optimal Nitrate Assimilation in the Cyanobacterium Anabaena sp. Strain PCC 7120

Puerta-Fernández

Vioque

2011

Journal of Bacteriology

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“…Hfq has recently emerged as a central player in post-transcriptional gene regulation as mediated by bacterial ncRNAs [3][4][5][6] . Escherichia coli Hfq mutants show disrupted signaling in stress response pathways 7,8 , arising from the need for Hfq to mediate base-pairing between regulatory ncRNAs and their mRNA targets.…”

Section: Introductionmentioning

confidence: 99%

Escherichia coli Hfq has distinct interaction surfaces for DsrA, rpoS and poly(A) RNAs

Mikulecky

Kaw

Brescia

et al. 2004

Nat Struct Mol Biol

226

395

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The bacterial Sm-like protein Hfq facilitates RNA-RNA interactions involved in posttranscriptional regulation of the stress response. Specifically, Hfq helps pair noncoding RNAs (ncRNAs) with complementary regions of target mRNAs. To probe the mechanism of this pairing, we generated a series of Hfq mutants and measured their affinity for RNAs like those with which Hfq must associate in vivo. We tested the mutants' DsrA-dependent activation of rpoS, and their ability to stabilize DsrA ncRNA against degradation in vivo. Our results suggest that Hfq has two independent RNA-binding surfaces. In addition to a well-known site around the core of the Hfq hexamer, we observe interactions with the distal face of Hfq, a new locus with which mRNAs and poly(A) sequences associate. Our model explains how Hfq can simultaneously bind a ncRNA and its mRNA target to facilitate the strand displacement reaction required for Hfq-dependent translational regulation.Hfq protein from Escherichia coli was first described in connection with Qβ-phage replication 1,2 . Hfq has recently emerged as a central player in post-transcriptional gene regulation as mediated by bacterial ncRNAs [3][4][5][6] . Escherichia coli Hfq mutants show disrupted signaling in stress response pathways 7,8 , arising from the need for Hfq to mediate base-pairing between regulatory ncRNAs and their mRNA targets. Examples of these partnerships include DsrA-rpoS 7,9,10 , OxyS-fhlA 11,12 , OxyS-rpoS 13 , RprA-rpoS 14 , RyhBsodB [15][16][17] .Complexes between ncRNAs and their mRNA targets function in several ways. Most commonly, complexed structures lead to translational activation or repression by remodeling mRNA regulatory regions containing the ribosome-binding site (RBS) and/or start codon. Alternatively, the interaction can enhance decay of the target mRNA16 or simply block translation11. Clearly, Hfq facilitates base-pairing between ncRNAs and their targets, but how it does so is poorly understood. How the chaperone function relates to other Hfq activities such as the control of poly(A) tail elongation19 , 20 and regulation of mRNA stability21 , 22 is also unknown. COMPETING INTERESTS STATEMENTThe authors declare that they have no competing financial interests. NIH Public Access Author ManuscriptNat Struct Mol Biol. Author manuscript; available in PMC 2011 April 5. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptHfq shares sequence similarity to the eukaryotic Lsm proteins [23][24][25][26][27] We addressed these questions through a mutational analysis of Hfq, probing in vitro binding to several model RNAs that represent species with which Hfq must interact. Hfq mutants were assayed in vivo using a reporter assay and RNA lifetime experiments. Together, the results support a model wherein at least two independent RNA-binding sites exist on the Hfq hexamer, and juxtaposition of bound RNAs facilitates base-pairing. RESULTS Hfq mutagenesisTo identify amino acids essential for RNA binding, we constructed a series of E. coli Hfq misse...

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“…Since the half-life of bacterial mRNA is strongly affected by the association with ribosomes (Deana and Belasco 2005), translation inhibition will promote the decay of the repressed target; e.g., by accelerating RNase E-mediated mRNA turnover (Massé et al 2003;Morita et al 2005). Besides RNase E, the bacterial Sm-like protein Hfq has been identified as a key player in this type of translational silencing (Valentin-Hansen et al 2004). Hfq binds all of the aforementioned sRNAs with high affinity and is most often required for both their intracellular stability and their interaction with target mRNAs (Zhang et al 2003;Aiba 2007;Urban and Vogel 2007, and references therein).…”

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confidence: 99%

A small RNA regulates multiple ABC transporter mRNAs by targeting C/A-rich elements inside and upstream of ribosome-binding sites

Sharma¹,

Darfeuille²,

Plantinga³

et al. 2007

Genes Dev.

342

479

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The interactions of numerous regulatory small RNAs (sRNAs) with target mRNAs have been characterized, but how sRNAs can regulate multiple, structurally unrelated mRNAs is less understood. Here we show that Salmonella GcvB sRNA directly acts on seven target mRNAs that commonly encode periplasmic substrate-binding proteins of ABC uptake systems for amino acids and peptides. Alignment of GcvB homologs of distantly related bacteria revealed a conserved G/U-rich element that is strictly required for GcvB target recognition. Analysis of target gene fusion regulation in vivo, and in vitro structure probing and translation assays showed that GcvB represses its target mRNAs by binding to extended C/A-rich regions, which may also serve as translational enhancer elements. In some cases (oppA, dppA), GcvB repression can be explained by masking the ribosome-binding site (RBS) to prevent 30S subunit binding. However, GcvB can also effectively repress translation by binding to target mRNAs at upstream sites, outside the RBS. Specifically, GcvB represses gltI mRNA translation at the C/A-rich target site located at positions −57 to −45 relative to the start codon. Taken together, our study suggests highly conserved regions in sRNAs and mRNA regions distant from Shine-Dalgarno sequences as important elements for the identification of sRNA targets.[Keywords: Small RNA; riboregulator; post-transcriptional control; translation inhibition; ABC transporter; GcvB] Supplemental material is available at http://www.genesdev.org.

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MicroReview: The bacterial Sm‐like protein Hfq: a key player in RNA transactions

Cited by 458 publications

References 55 publications

Hfq Is Required for Optimal Nitrate Assimilation in the Cyanobacterium Anabaena sp. Strain PCC 7120

Hfq Is Required for Optimal Nitrate Assimilation in the Cyanobacterium Anabaena sp. Strain PCC 7120

Escherichia coli Hfq has distinct interaction surfaces for DsrA, rpoS and poly(A) RNAs

A small RNA regulates multiple ABC transporter mRNAs by targeting C/A-rich elements inside and upstream of ribosome-binding sites

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