Formation of DNA:RNA Hybrid G‐Quadruplex in Bacterial Cells and Its Dominance over the Intramolecular DNA G‐Quadruplex in Mediating Transcription Termination

Wu, Renyi; Zheng, Ke-wei; Zhang, Jiayu; Hao, Yu-hua; Tan, Zheng

doi:10.1002/anie.201408719

Cited by 49 publications

(50 citation statements)

References 20 publications

(19 reference statements)

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“…To this end, G4 structures are pausing sites for the polymerases, which ultimately result in the termination of transcription [109,110]. In this model, G4 structures can be formed by the RNA transcript [111] or by a DNA-RNA hybrid [112][113][114]. A good candidate for regulating this mechanism is the DEAH box helicase DHX9.…”

Section: Effects Of Helicases Acting On G4 Structures During Transcrimentioning

confidence: 99%

G-quadruplex unwinding helicases and their function in vivo

Sauer

Paeschke

2017

Biochemical Society Transactions

140

139

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The concept that G-quadruplex (G4) structures can form within DNA or RNA has been long known and extensively discussed. In recent years, accumulating evidences imply that G-quadruplex structures form Initially, inefficient regulation of G-quadruplex structures was mainly associated with genome instability. However, due to the location of G-quadruplex motifs and their evolutionary conservation, different cellular functions of these structures have been postulated (e.g. in telomere maintenance, DNA replication, transcription, and translation). Regardless of their function, efficient and controlled formation and unwinding are very important, because 'mis'-regulated G-quadruplex structures are detrimental for a given process, causing genome instability and diseases. Several helicases have been shown to target and regulate specific G-quadruplex structures. This mini-review focuses on the biological consequences of G4 disruption by different helicases .

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Section: Effects Of Helicases Acting On G4 Structures During Transcrimentioning

confidence: 99%

G-quadruplex unwinding helicases and their function in vivo

Sauer

Paeschke

2017

Biochemical Society Transactions

140

139

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“…Reports vary as to the assessment of the potential for the participation of G-quadruplex structures in the regulation of gene expression in E. coli [13,14,18,19]. As demonstrated by Duquette et al, certain human sequences can form G-quadruplexes in E. coli [20], and G-quadruplex formation in mRNA can influence bacterial message utilization [21,22].…”

Section: Introductionmentioning

confidence: 99%

Role of Hfq in Genome Evolution: Instability of G-Quadruplex Sequences in E. coli

et al. 2019

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Certain G-rich DNA repeats can form quadruplex in bacterial chromatin that can present blocks to DNA replication and, if not properly resolved, may lead to mutations. To understand the participation of quadruplex DNA in genomic instability in Escherichia coli (E. coli), mutation rates were measured for quadruplex-forming DNA repeats, including (G 3 T) 4 , (G 3 T) 8 , and a RET oncogene sequence, cloned as the template or nontemplate strand. We evidence that these alternative structures strongly influence mutagenesis rates. Precisely, our results suggest that G-quadruplexes form in E. coli cells, especially during transcription when the G-rich strand can be displaced by R-loop formation. Structure formation may then facilitate replication misalignment, presumably associated with replication fork blockage, promoting genomic instability. Furthermore, our results also evidence that the nucleoid-associated protein Hfq is involved in the genetic instability associated with these sequences. Hfq binds and stabilizes G-quadruplex structure in vitro and likely in cells. Collectively, our results thus implicate quadruplexes structures and Hfq nucleoid protein in the potential for genetic change that may drive evolution or alterations of bacterial gene expression. variable with strands arranged in a parallel, antiparallel, or mixed orientations associated with various glycosidic configurations of guanines [1,[3][4][5]. A single repeat motif can often form multiple structures depending on ionic conditions, as shown for repeats at human telomeres and oncogene promoters [4][5][6][7]. When G-quadruplex structures form in duplex DNA, the C-rich DNA strand complementary to G-quadruplex-forming sequences can form a four stranded i-motif at low pH [8], in which two tracts of cytosines form interdigitated C•C + base pairs [7,9,10] (Figure 1C).Microorganisms 2019, 7, x 2 of 16 quartets are stabilized by monovalent cations. The topology of quadruplex structures is highly variable with strands arranged in a parallel, antiparallel, or mixed orientations associated with various glycosidic configurations of guanines [1,[3][4][5]. A single repeat motif can often form multiple structures depending on ionic conditions, as shown for repeats at human telomeres and oncogene promoters [4][5][6][7]. When G-quadruplex structures form in duplex DNA, the C-rich DNA strand complementary to G-quadruplex-forming sequences can form a four stranded i-motif at low pH [8], in which two tracts of cytosines form interdigitated C•C + base pairs [7,9,10] (Figure 1C).

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“…In bacteria, G4s of DNA are widely distributed, conserved, and enriched in regulatory regions that perform critical functions in replication (30), transcription (31)(32)(33)(34), and translation (32). A DNA-RNA hybrid G-quadruplex formed in bacterial cells mediates transcription termination (35). The stabilization of G-quadruplex in the gene promoter region affects gene transcription (36).…”

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confidence: 99%

RNA G-Quadruplex Structures Mediate Gene Regulation in Bacteria

Shao

Zhang

Umar

et al. 2020

mBio

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Guanine (G)-rich sequences in RNA can fold into diverse RNA G-quadruplex (rG4) structures to mediate various biological functions and cellular processes in eukaryotic organisms. However, the presence, locations, and functions of rG4s in prokaryotes are still elusive. We used QUMA-1, an rG4-specific fluorescent probe, to detect rG4 structures in a wide range of bacterial species both in vitro and in live cells and found rG4 to be an abundant RNA secondary structure across those species. Subsequently, to identify bacterial rG4 sites in the transcriptome, the model Escherichia coli strain and a major human pathogen, Pseudomonas aeruginosa, were subjected to recently developed high-throughput rG4 structure sequencing (rG4-seq). In total, 168 and 161 in vitro rG4 sites were found in E. coli and P. aeruginosa, respectively. Genes carrying these rG4 sites were found to be involved in virulence, gene regulation, cell envelope synthesis, and metabolism. More importantly, biophysical assays revealed the formation of a group of rG4 sites in mRNAs (such as hemL and bswR), and they were functionally validated in cells by genetic (point mutation and lux reporter assays) and phenotypic experiments, providing substantial evidence for the formation and function of rG4s in bacteria. Overall, our study uncovers important regulatory functions of rG4s in bacterial pathogenicity and metabolic pathways and strongly suggests that rG4s exist and can be detected in a wide range of bacterial species. IMPORTANCE G-quadruplex in RNA (rG4) mediates various biological functions and cellular processes in eukaryotic organisms. However, the presence, locations, and functions of rG4 are still elusive in prokaryotes. Here, we found that rG4 is an abundant RNA secondary structure across a wide range of bacterial species. Subsequently, the transcriptome-wide rG4 structure sequencing (rG4-seq) revealed that the model E. coli strain and a major human pathogen, P. aeruginosa, have 168 and 161 in vitro rG4 sites, respectively, involved in virulence, gene regulation, cell envelope, and metabolism. We further verified the regulatory functions of two rG4 sites in bacteria (hemL and bswR). Overall, this finding strongly suggests that rG4s play key regulatory roles in a wide range of bacterial species.

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Formation of DNA:RNA Hybrid G‐Quadruplex in Bacterial Cells and Its Dominance over the Intramolecular DNA G‐Quadruplex in Mediating Transcription Termination

Cited by 49 publications

References 20 publications

G-quadruplex unwinding helicases and their function in vivo

G-quadruplex unwinding helicases and their function in vivo

Role of Hfq in Genome Evolution: Instability of G-Quadruplex Sequences in E. coli

RNA G-Quadruplex Structures Mediate Gene Regulation in Bacteria

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