Hfq: the flexible RNA matchmaker

Updegrove, Taylor B.; Zhang, Aixia; Storz, Gisela

doi:10.1016/j.mib.2016.02.003

Cited by 286 publications

(260 citation statements)

References 45 publications

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“…Its central component, the RNA binding protein CsrA (RsmA), was uncovered by a transposon mutagenesis screen designed to identify regulators of gene expression in the stationary phase of growth, using glycogen biosynthesis and glgC’-‘lacZ expression as reporters (1). Understanding of RNA binding proteins and their roles in regulation was limited at that time, but included Hfq and ribosomal proteins that mediate negative feedback by binding to their mRNAs (2–4). Soon after its discovery, the regulatory role of CsrA began to emerge, which included repression of other genes similar to glgC , which are expressed in stationary phase or under stress conditions (5), and evidence that CsrA activates gene expression that supports robust growth (6).…”

Section: Inroductionmentioning

confidence: 99%

Global Regulation by CsrA and Its RNA Antagonists

Romeo

Babitzke²

2018

Microbiol Spectr

147

145

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The sequence-specific RNA binding protein CsrA is employed by diverse bacteria in the posttranscriptional regulation of gene expression. Its binding interactions with RNA have been documented at atomic resolution and shown to alter RNA secondary structure, RNA stability, translation and/or Rho-mediated transcription termination through a growing number of molecular mechanisms. In Gammaproteobacteria, small regulatory RNAs that contain multiple CsrA binding sites compete with mRNA for binding to CsrA, thereby sequestering and antagonizing this protein. Both the synthesis and turnover of these sRNAs are regulated, allowing CsrA activity to be rapidly and efficiently adjusted in response to nutritional conditions and stresses. Feedback loops between the Csr regulatory components improve the dynamics of signal response by the Csr system. The Csr system of E. coli is intimately interconnected with other global regulatory systems, permitting it to contribute to regulation by those systems. In some species, a protein antagonist of CsrA functions as part of a checkpoint for flagellum biosynthesis. In other species, a protein antagonist participates in a mechanism in which a type III secretion system is used for sensing interactions with host cells. Recent transcriptomics studies reveal vast effects of CsrA on gene expression through direct binding to hundreds of mRNAs, and indirectly through its effects on the expression of dozens of transcription factors. CsrA binding to basepairing sRNAs and novel mRNA segments, such as the 3′ UTR and deep within coding regions, predict its participation in yet to be discovered regulatory mechanisms.

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Section: Inroductionmentioning

confidence: 99%

Global Regulation by CsrA and Its RNA Antagonists

Romeo

Babitzke²

2018

Microbiol Spectr

147

145

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“…Overall, this whole 30-nt long sequence contains 18 adenosines and eight uridines. The Hfq binding sites identified previously in mRNAs included both the ARN repeats (Soper and Woodson 2008;Link et al 2009;Beisel et al 2012) and the AU-rich regions Updegrove et al 2016). However, it was recently proposed that there is a continuum of possible interactions of Hfq with different RNA sequences .…”

mentioning

confidence: 94%

“…The Hfq protein is involved in the regulation of translation by bacterial small RNAs (sRNAs) (Updegrove et al 2016). These noncoding RNAs recognize complementary sequences in their target mRNAs, and induce the activation or repression of translation (Waters and Storz 2009;Updegrove et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Hfq assists small RNAs in binding to the coding sequence of ompD mRNA and in rearranging its structure

Wróblewska

Olejniczak

2016

RNA

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The bacterial protein Hfq participates in the regulation of translation by small noncoding RNAs (sRNAs). Several mechanisms have been proposed to explain the role of Hfq in the regulation by sRNAs binding to the 5 ′ -untranslated mRNA regions. However, it remains unknown how Hfq affects those sRNAs that target the coding sequence. Here, the contribution of Hfq to the annealing of three sRNAs, RybB, SdsR, and MicC, to the coding sequence of Salmonella ompD mRNA was investigated. Hfq bound to ompD mRNA with tight, subnanomolar affinity. Moreover, Hfq strongly accelerated the rates of annealing of RybB and MicC sRNAs to this mRNA, and it also had a small effect on the annealing of SdsR. The experiments using truncated RNAs revealed that the contributions of Hfq to the annealing of each sRNA were individually adjusted depending on the structures of interacting RNAs. In agreement with that, the mRNA structure probing revealed different structural contexts of each sRNA binding site. Additionally, the annealing of RybB and MicC sRNAs induced specific conformational changes in ompD mRNA consistent with local unfolding of mRNA secondary structure. Finally, the mutation analysis showed that the long AU-rich sequence in the 5 ′ -untranslated mRNA region served as an Hfq binding site essential for the annealing of sRNAs to the coding sequence. Overall, the data showed that the functional specificity of Hfq in the annealing of each sRNA to the ompD mRNA coding sequence was determined by the sequence and structure of the interacting RNAs.

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“…This chapter, however, will focus on RNA binding proteins that “passively” remodel RNA structures without hydrolyzing ATP. In bacteria, this type of passive RNA chaperone includes cold shock proteins (CSPs) (14), the Sm family protein Hfq (21), the FinO/ProQ family of RNA binding proteins (22), and ribosomal proteins S1 (23–25) and S12 (26). H-NS and StpA, which interact with the bacterial nucleoid, also possess RNA chaperone activity (17).…”

Section: Introductionmentioning

confidence: 99%

“…Stable anti-sense binding depends on the rearrangement of adjacent nucleotides to extend the intermolecular base pairing (52, 54, 55), which for colE1 is facilitated by the Rop/Rom protein (56). In an analogous fashion, trans-acting small RNAs depend on chaperone proteins like Hfq to initiate base pairing, facilitate strand exchange, and destabilize self-structure that can mask complementary regions in the sRNA and the target RNA (9, 21). …”

Section: Introductionmentioning

confidence: 99%

Proteins That Chaperone RNA Regulation

Woodson¹,

Panja²,

Santiago-Frangos

2018

Microbiol Spectr

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RNA-binding proteins chaperone the biological functions of non-coding RNA by reducing RNA misfolding, improving matchmaking between regulatory RNA and targets, and exerting quality control over RNP biogenesis. Recent studies of E. coli CspA, HIV NCp and E. coli Hfq, are beginning to show how RNA-binding proteins remodel RNA structures. These different protein families use common strategies for disrupting or annealing RNA double helices, which can be used to understand the mechanisms by which proteins chaperone RNA-dependent regulation in bacteria.

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Hfq: the flexible RNA matchmaker

Cited by 286 publications

References 45 publications

Global Regulation by CsrA and Its RNA Antagonists

Global Regulation by CsrA and Its RNA Antagonists

Hfq assists small RNAs in binding to the coding sequence of ompD mRNA and in rearranging its structure

Proteins That Chaperone RNA Regulation

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