Modulating endogenous gene expression of mammalian cells via RNA–small molecule interaction

Tuleuova, Nazgul; An, Chung Il; Ramanculov, Erlan; Revzin, Alexander; Yokobayashi, Yohei

doi:10.1016/j.bbrc.2008.08.112

Cited by 40 publications

(29 citation statements)

References 23 publications

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“…1)1920. To construct the ON system in human cells, we designed and constructed a synthetic shRNA293031 containing an siRNA and the Kt motif in its stem and loop regions, respectively (Figs 1 and 3a; Supplementary Fig. S6).…”

Section: Resultsmentioning

confidence: 99%

Synthetic human cell fate regulation by protein-driven RNA switches

et al. 2011

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Understanding how to control cell fate is crucial in biology, medical science and engineering. In this study, we introduce a method that uses an intracellular protein as a trigger for regulating human cell fate. The ON/OFF translational switches, composed of an intracellular protein L7Ae and its binding RNA motif, regulate the expression of a desired target protein and control two distinct apoptosis pathways in target human cells. Combined use of the switches demonstrates that a specific protein can simultaneously repress and activate the translation of two different mRNAs: one protein achieves both up- and downregulation of two different proteins/pathways. A genome-encoded protein fused to L7Ae controlled apoptosis in both directions (death or survival) depending on its cellular expression. The method has potential for curing cellular defects or improving the intracellular production of useful molecules by bypassing or rewiring intrinsic signal networks.

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Section: Resultsmentioning

confidence: 99%

Synthetic human cell fate regulation by protein-driven RNA switches

et al. 2011

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“…However, this system is restricted to gene regulation in bacteria since regulation involves sequestration of the bacterial ribosomal binding site (30,31). Conditional gene expression by RNAi controlled by aptamers has also been shown (32,33). However a specific design of the regulating elements is needed for each new gene.…”

Section: Discussionmentioning

confidence: 99%

A fast and efficient translational control system for conditional expression of yeast genes

Kötter

Weigand

Meyer

et al. 2009

Nucleic Acids Research

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A new artificial regulatory system for essential genes in yeast is described. It prevents translation of target mRNAs upon tetracycline (tc) binding to aptamers introduced into their 5′UTRs. Exploiting direct RNA–ligand interaction renders auxiliary protein factors unnecessary. Therefore, our approach is strain independent and not susceptible to interferences by heterologous expressed regulatory proteins. We use a simple PCR-based strategy, which allows easy tagging of any target gene and the level of gene expression can be adjusted due to various tc aptamer-regulated promoters. As proof of concept, five differently expressed genes were targeted, two of which could not be regulated previously. In all cases, adding tc completely prevented growth and, as shown for Nop14p, rapidly abolished de novo protein synthesis providing a powerful tool for conditional regulation of yeast gene expression.

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“…The Pei group adapted another Drosha modulation strategy originally reported by our group [36,37] to control endogenous gene expression in cancer cell lines to induce apoptosis. A theophylline activated aptazyme was inserted between an inhibitory strand that blocks the 3 0 single-stranded region of the pri-miRNA, thereby preventing the RNA from being processed by Drosha (Figure 3d).…”

Section: Controlling Microrna Maturation Pathway By Aptamersmentioning

confidence: 99%

Aptamer-based and aptazyme-based riboswitches in mammalian cells

Yokobayashi

2019

Current Opinion in Chemical Biology

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Molecular recognition by RNA aptamers has been exploited to control gene expression in response to small molecules in mammalian cells. These mammalian synthetic riboswitches offer attractive features such as small genetic size and lower risk of immunological complications compared to proteinbased transcriptional gene switches. The diversity of gene regulatory mechanisms that involve RNA has also inspired the development of mammalian riboswitches that harness various regulatory mechanisms. In this report, recent advances in synthetic riboswitches that function in mammalian cells are reviewed focusing on the regulatory mechanisms they exploit such as mRNA degradation, microRNA processing, and programmed ribosomal frameshifting.

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Modulating endogenous gene expression of mammalian cells via RNA–small molecule interaction

Cited by 40 publications

References 23 publications

Synthetic human cell fate regulation by protein-driven RNA switches

Synthetic human cell fate regulation by protein-driven RNA switches

A fast and efficient translational control system for conditional expression of yeast genes

Aptamer-based and aptazyme-based riboswitches in mammalian cells

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