NanoRNAs: A Class of Small RNAs That Can Prime Transcription Initiation in Bacteria

Nickels, Bryce E.; Dove, Simon L.

doi:10.1016/j.jmb.2011.06.015

Cited by 33 publications

(25 citation statements)

References 68 publications

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“…NanoRNAs are converted to mononucleotides by the highly conserved oligoribonuclease Orn (389), which may represent the enigmatic PDE-B protein. Interestingly, Orn was least active against a GpG dinucleotide compared to a panel of other tested dinucleotides (390). This suggests that the half-life of pGpG may be prolonged selectively in vivo to allow priming of transcription.…”

Section: Open Questions In C-di-gmp Signalingmentioning

confidence: 98%

Cyclic di-GMP: the First 25 Years of a Universal Bacterial Second Messenger

Römling

Galperin

Gomelsky

2013

Microbiol Mol Biol Rev

1,484

1,698

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SUMMARY Twenty-five years have passed since the discovery of cyclic dimeric (3′→5′) GMP (cyclic di-GMP or c-di-GMP). From the relative obscurity of an allosteric activator of a bacterial cellulose synthase, c-di-GMP has emerged as one of the most common and important bacterial second messengers. Cyclic di-GMP has been shown to regulate biofilm formation, motility, virulence, the cell cycle, differentiation, and other processes. Most c-di-GMP-dependent signaling pathways control the ability of bacteria to interact with abiotic surfaces or with other bacterial and eukaryotic cells. Cyclic di-GMP plays key roles in lifestyle changes of many bacteria, including transition from the motile to the sessile state, which aids in the establishment of multicellular biofilm communities, and from the virulent state in acute infections to the less virulent but more resilient state characteristic of chronic infectious diseases. From a practical standpoint, modulating c-di-GMP signaling pathways in bacteria could represent a new way of controlling formation and dispersal of biofilms in medical and industrial settings. Cyclic di-GMP participates in interkingdom signaling. It is recognized by mammalian immune systems as a uniquely bacterial molecule and therefore is considered a promising vaccine adjuvant. The purpose of this review is not to overview the whole body of data in the burgeoning field of c-di-GMP-dependent signaling. Instead, we provide a historic perspective on the development of the field, emphasize common trends, and illustrate them with the best available examples. We also identify unresolved questions and highlight new directions in c-di-GMP research that will give us a deeper understanding of this truly universal bacterial second messenger.

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Section: Open Questions In C-di-gmp Signalingmentioning

confidence: 98%

Cyclic di-GMP: the First 25 Years of a Universal Bacterial Second Messenger

Römling

Galperin

Gomelsky

2013

Microbiol Mol Biol Rev

1,484

1,698

View full text Add to dashboard Cite

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“…As a consequence, pGpG can compete for c-di-GMP binding to inhibit RocR activity, leading to the observed increase in c-di-GMP concentration. There are two potential sources of pGpG in the cell: linearization of c-di-GMP and normal RNA processing and turnover (69). Future studies will determine the relative contribution of each source.…”

Section: 6mentioning

confidence: 99%

Oligoribonuclease is the primary degradative enzyme for pGpG in Pseudomonas aeruginosa that is required for cyclic-di-GMP turnover

Orr

Donaldson

Severin

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

120

142

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The bacterial second messenger cyclic di-GMP (c-di-GMP) controls biofilm formation and other phenotypes relevant to pathogenesis. Cyclic-di-GMP is synthesized by diguanylate cyclases (DGCs). Phosphodiesterases (PDE-As) end signaling by linearizing c-di-GMP to 5ʹ-phosphoguanylyl-(3ʹ,5ʹ)-guanosine (pGpG), which is then hydrolyzed to two GMP molecules by yet unidentified enzymes termed PDE-Bs. We show that pGpG inhibits a PDE-A from Pseudomonas aeruginosa. In a dual DGC and PDE-A reaction, excess pGpG extends the half-life of c-di-GMP, indicating that removal of pGpG is critical for c-di-GMP homeostasis. Thus, we sought to identify the PDE-B enzyme(s) responsible for pGpG degradation. A differential radial capillary action of ligand assay-based screen for pGpG binding proteins identified oligoribonuclease (Orn), an exoribonuclease that hydrolyzes two-to five-nucleotide-long RNAs. Purified Orn rapidly converts pGpG into GMP. To determine whether Orn is the primary enzyme responsible for degrading pGpG, we assayed cell lysates of WT and Δorn strains of P. aeruginosa PA14 for pGpG stability. The lysates from Δorn showed 25-fold decrease in pGpG hydrolysis. Complementation with WT, but not active site mutants, restored hydrolysis. Accumulation of pGpG in the Δorn strain could inhibit PDE-As, increasing c-di-GMP concentration. In support, we observed increased transcription from the c-di-GMP-regulated pel promoter. Additionally, the c-di-GMP-governed auto-aggregation and biofilm phenotypes were elevated in the Δorn strain in a pel-dependent manner. Finally, we directly detect elevated pGpG and c-di-GMP in the Δorn strain. Thus, we identified that Orn serves as the primary PDE-B enzyme that removes pGpG, which is necessary to complete the final step in the c-di-GMP degradation pathway.cyclic di-GMP | oligoribonuclease | pGpG | PDE-B | nanoRNase

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“…Orn activity was shown to be essential in E. coli (Ghosh & Deutscher, 1999). When accumulated, nanoRNA can be used to prime transcription initiation and alter global gene expression (Goldman et al, 2011;Nickels & Dove, 2011). NanoRNase activity of Orn and its human homologue, Sfn, was shown to be inhibited by 39-phosphoadenosine 59-phosphate (pAp) in vitro (Mechold et al, 2006).…”

Section: Introductionmentioning

confidence: 99%