RNA as a Versatile and Powerful Platform for Engineering Genetic Regulatory Tools

Win, Maung Nyan; Smolke, Christina D.

doi:10.1080/02648725.2007.10648106

Cited by 26 publications

(13 citation statements)

References 194 publications

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“…The same holds for RNA interference. Recent attempts to control gene expression with antisense RNA were made in yeast metabolic engineering (31,153 (389). The importance of RNA techniques for yeast metabolic engineering will undoubtedly increase in the future.…”

Section: Changing Protein Cellular Levelsmentioning

confidence: 99%

Progress in Metabolic Engineering of Saccharomyces cerevisiae

Nevoigt

2008

Microbiol Mol Biol Rev

521

333

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SUMMARY The traditional use of the yeast Saccharomyces cerevisiae in alcoholic fermentation has, over time, resulted in substantial accumulated knowledge concerning genetics, physiology, and biochemistry as well as genetic engineering and fermentation technologies. S. cerevisiae has become a platform organism for developing metabolic engineering strategies, methods, and tools. The current review discusses the relevance of several engineering strategies, such as rational and inverse metabolic engineering, evolutionary engineering, and global transcription machinery engineering, in yeast strain improvement. It also summarizes existing tools for fine-tuning and regulating enzyme activities and thus metabolic pathways. Recent examples of yeast metabolic engineering for food, beverage, and industrial biotechnology (bioethanol and bulk and fine chemicals) follow. S. cerevisiae currently enjoys increasing popularity as a production organism in industrial (“white”) biotechnology due to its inherent tolerance of low pH values and high ethanol and inhibitor concentrations and its ability to grow anaerobically. Attention is paid to utilizing lignocellulosic biomass as a potential substrate.

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Section: Changing Protein Cellular Levelsmentioning

confidence: 99%

Progress in Metabolic Engineering of Saccharomyces cerevisiae

Nevoigt

2008

Microbiol Mol Biol Rev

521

333

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“…Studies on gene-specific silencing by RNA have made great progress in elucidating both the mechanisms and potential applications of this technology (Win et al 2007) since RNAi (gene silencing by double-stranded RNA) was discovered in Caenorhabditis elegans (Fire et al 1998). Although this phenomenon has now been described for many different eukaryotes, the existence of RNAi in prokaryotes is still a hypothesis based on computational analysis (Makarova et al 2006).…”

Section: Introductionmentioning

confidence: 97%

Gene-specific silencing induced by parallel complementary RNA in Pseudomonas aeruginosa

et al. 2009

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To investigate whether parallel complementary RNA (pRNA) could induce gene-specific silencing in Pseudomonas aeruginosa, pRNA of the mexA gene was expressed in it. Compared to the control strains, the strain expressing pRNA of mexA showed a 50% decrease in minimum inhibitory concentrations (MICs) of several antimicrobial agents and a twofold increase in the initial accumulation rate of ethidium bromide, all of which are substrates of the MexAB-OprM efflux pump. These results suggest that gene-specific silencing was induced by pRNA. This is the first time that such a route for gene silencing has been reported in a bacterium other than Escherichia coli. Gene-specific silencing induced by pRNA may be useful as a novel biotechnology tool for gene regulation in prokaryotes.

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“…In addition, naturally occurring, functional RNAs have been engineered to fulfil novel tasks. [16,17] RNAs represent ideal tools to implement synthetic RNA interference is triggered by small hairpin precursors that are processed by the endonuclease dicer to yield active species such as siRNAs and miRNAs. To regulate the RNAi-mediated suppression of gene expression, we imagined a strategy that relies on the sequence-specific inhibition of shRNA precursor processing by immediate RNA-small molecule interactions.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Dicing of Guanosine‐Rich shRNAs by Quadruplex‐Binding Compounds

et al. 2008

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RNA interference is triggered by small hairpin precursors that are processed by the endonuclease dicer to yield active species such as siRNAs and miRNAs. To regulate the RNAi-mediated suppression of gene expression, we imagined a strategy that relies on the sequence-specific inhibition of shRNA precursor processing by immediate RNA-small molecule interactions. Here, we present a first step in this direction by augmenting shRNAs with guanosine-rich sequences that are prone to fold into four-stranded structures. The addition of small molecules that selectively bind to such quadruplex sequences should allow for the specific inhibition of dicing of shRNAs that contain suitable G-rich elements. In an attempt to find compounds that protect against dicer processing, we have examined the effects of quadruplex-binding compounds on the dicer processing of shRNAs containing G-quadruplexes. Although a variety of small molecules that are known to bind to quadruplexes inhibited in vitro dicing of shRNAs, only two substance classes, namely certain porphyrazines and bisquinolinium compounds, showed selective inhibition of G-rich shRNAs compared to control sequences lacking guanine-rich elements. The G-rich shRNAs displayed a potent knockdown of gene expression in mammalian cell culture, but the effect was not influenced by addition of the respective quadruplex-binding compounds.

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RNA as a Versatile and Powerful Platform for Engineering Genetic Regulatory Tools

Cited by 26 publications

References 194 publications

Progress in Metabolic Engineering of Saccharomyces cerevisiae

Progress in Metabolic Engineering of Saccharomyces cerevisiae

Gene-specific silencing induced by parallel complementary RNA in Pseudomonas aeruginosa

Inhibition of Dicing of Guanosine‐Rich shRNAs by Quadruplex‐Binding Compounds

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