RNA with iron(II) as a cofactor catalyses electron transfer

Hsiao, Chiaolong; Chou, I-Chun; Okafor, C. Denise; Bowman, Jessica C.; O’Neill, Eric B.; Athavale, Shreyas S.; Petrov, Anton S.; Hud, Nicholas V.; Wartell, Roger M.; Harvey, Stephen C.; Williams, Loren Dean

doi:10.1038/nchem.1649

Cited by 71 publications

(51 citation statements)

References 31 publications

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“…These Mg 2+ ions are exposed to the solvent side of the large subunit allowing their potential replacement with Fe 2+ . In support of iron binding by rRNA, previous studies have shown that Fe 2+ , being a divalent cation with similar ionic radii and geometric properties as Mg 2+ , is capable of structural and functional replacement of Mg 2+ in nucleic acids (33,37,(52)(53)(54)(55). It is clear, however, that not every Mg 2+ ion bound to the ribosome could be substituted by iron with the same efficiency.…”

Section: Discussionmentioning

confidence: 85%

Iron-dependent cleavage of ribosomal RNA during oxidative stress in the yeast Saccharomyces cerevisiae

Zinskie

Ghosh

Trainor

et al. 2018

Journal of Biological Chemistry

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Stress-induced strand breaks in rRNA have been observed in many organisms, but the mechanisms by which they originate are not well understood. Here, we show that a chemical rather than enzymatic mechanism initiates rRNA cleavages during oxidative stress in yeast (Saccharomyces cerevisiae). We used cells lacking the mitochondrial glutaredoxin Grx5 to demonstrate that oxidant-induced cleavage formation in 25S rRNA correlates with intracellular iron levels. Sequestering free iron by a chemical or genetic means decreased the extent of rRNA degradation and relieved the hypersensitivity of grx5 cells to the oxidants. Importantly, subjecting purified ribosomes to an in vitro iron/ascorbate reaction precisely recapitulated the 25S rRNA cleavage pattern observed in cells, indicating that redox activity of the ribosome-bound iron is responsible for the strand breaks in the rRNA. In summary, our findings provide evidence that oxidative stress-associated rRNA cleavages can occur through rRNA strand scission by redox-active, ribosomebound iron that potentially promotes Fenton reaction-induced hydroxyl radical production, implicating intracellular iron as a key determinant of the effects of oxidative stress on ribosomes. We propose that iron binding to specific ribosome elements primes rRNA for cleavages that may play a role in redox-sensitive tuning of the ribosome function in stressed cells.

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Section: Discussionmentioning

confidence: 85%

Iron-dependent cleavage of ribosomal RNA during oxidative stress in the yeast Saccharomyces cerevisiae

Zinskie

Ghosh

Trainor

et al. 2018

Journal of Biological Chemistry

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“…While most respiratory enzymes contain a large number of cofactors that contain iron, including complex I that has up to nine Fe-S centers [77], Na + -NQR contains only one 2Fe-2S center and four flavin molecules. Iron has been considered one of the key elements involved in the origin of life, probably forming part of the first cofactors in enzymatic reactions [78], [79]. The ability to use minimal amounts of iron could represent an early adaptation of primordial anaerobic cells to the rising levels of oxygen.…”

Section: Resultsmentioning

confidence: 99%

Origin and Evolution of the Sodium -Pumping NADH: Ubiquinone Oxidoreductase

2014

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The sodium -pumping NADH: ubiquinone oxidoreductase (Na+-NQR) is the main ion pump and the primary entry site for electrons into the respiratory chain of many different types of pathogenic bacteria. This enzymatic complex creates a transmembrane gradient of sodium that is used by the cell to sustain ionic homeostasis, nutrient transport, ATP synthesis, flagellum rotation and other essential processes. Comparative genomics data demonstrate that the nqr operon, which encodes all Na+-NQR subunits, is found in a large variety of bacterial lineages with different habitats and metabolic strategies. Here we studied the distribution, origin and evolution of this enzymatic complex. The molecular phylogenetic analyses and the organizations of the nqr operon indicate that Na+-NQR evolved within the Chlorobi/Bacteroidetes group, after the duplication and subsequent neofunctionalization of the operon that encodes the homolog RNF complex. Subsequently, the nqr operon dispersed through multiple horizontal transfer events to other bacterial lineages such as Chlamydiae, Planctomyces and α, β, γ and δ -proteobacteria. Considering the biochemical properties of the Na+-NQR complex and its physiological role in different bacteria, we propose a detailed scenario to explain the molecular mechanisms that gave rise to its novel redox- dependent sodium -pumping activity. Our model postulates that the evolution of the Na+-NQR complex involved a functional divergence from its RNF homolog, following the duplication of the rnf operon, the loss of the rnfB gene and the recruitment of the reductase subunit of an aromatic monooxygenase.

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“…The multiple functions of biological RNAs, and the expanding catalytic repertoire associated with RNA (Biondi et al 2012;Hsiao et al 2013;Johnston et al 2001;Turk et al 2010) lend credibility to the hypothesis that RNA served as both catalysts and selfreplicating information storage at the beginning of evolution (Gilbert 1986;Joyce 1989). Although evidence supporting this premise has accumulated, the fragility of RNA in aqueous solutions has been recognized as a difficulty for the emergence of self-replicating RNA (Bada and Lazcano 2002;Levy and Miller 1998;Li and Breaker 1999;Pace 1991).…”

Section: Introductionmentioning

confidence: 90%

Ligation of RNA Oligomers by the Schistosoma mansoni Hammerhead Ribozyme in Frozen Solution

et al. 2016

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The interstitial liquid phase within frozen aqueous solutions is an environment that minimizes RNA degradation and facilitates reactions that may have relevance to the RNA World hypothesis. Previous work has shown that frozen solutions support condensation of activated nucleotides into RNA oligomers, RNA ligation by the hairpin ribozyme, and RNA synthesis by a RNA polymerase ribozyme. In the current study, we examined the activity of a hammerhead ribozyme (HHR) in frozen solution. The Schistosoma mansoni hammerhead ribozyme, which predominantly cleaves RNA, can ligate its cleaved products (P1 and P2) with yields up to ~23 % in single turnover experiments at 25 °C in the presence of Mg(2+). Our studies show that this HHR ligates RNA oligomers in frozen solution in the absence of divalent cations. Citrate and other anions that exhibit strong ion-water affinity enhanced ligation. Yields up to 43 % were observed in one freeze-thaw cycle and a maximum of 60 % was obtained after several freeze-thaw cycles using wild-type P1 and P2. Truncated and mutated P1 substrates were ligated to P2 with yields of 14-24 % in one freeze-thaw cycle. A pool of P2 substrates with mixtures of all four bases at five positions were ligated with P1 in frozen solution. High-throughput sequencing indicated that 70 of the 1024 possible P2 sequences were represented in ligated products at 1000 or more read counts per million reads. The results indicate that the HHR can ligate a range of short RNA oligomers into an ensemble of diverse sequences in ice.

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RNA with iron(II) as a cofactor catalyses electron transfer

Cited by 71 publications

References 31 publications

Iron-dependent cleavage of ribosomal RNA during oxidative stress in the yeast Saccharomyces cerevisiae

Iron-dependent cleavage of ribosomal RNA during oxidative stress in the yeast Saccharomyces cerevisiae

Origin and Evolution of the Sodium -Pumping NADH: Ubiquinone Oxidoreductase

Ligation of RNA Oligomers by the Schistosoma mansoni Hammerhead Ribozyme in Frozen Solution

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