A Synthetic Riboswitch that Operates using a Rationally Designed Ligand–RNA Pair

Regulation of the heat shock response (HSR) is essential in all living systems. In E. coli, the HSR is regulated by an alternative s factor, s 32 , which is encoded by the rpoH gene. The mRNA of rpoH adopts a complex secondary structure that is critical for the proper translation of the s 32 protein. At low temperatures, the rpoH gene transcript forms a highly structured mRNA containing several three-way junctions, including a rare perfectly paired three-way junction (3WJ). This complex secondary structure serves as a primitive but highly effective strategy for the thermal control of gene expression. In this work, the first small-molecule modulators of the E. coli s 32 mRNA temperature sensor are reported.

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Modulation of the E. coli rpoH Temperature Sensor with Triptycene‐Based Small Molecules

Barros

Yoon

Chenoweth

2016

Angewandte Chemie

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Restoration of Ribozyme Tertiary Contact and Function by Using a Molecular Glue for RNA

2017

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Some RNAc lasses require folding into the proper higher-order structures to exert their functions.H ammerhead ribozyme (HHR) requires af olding conformation stabilized by tertiary interaction for full activity.Arationally engineered HHR was developed that was inactive,b ut could be activated by as ynthetic RNA-binding ligand, naphthyridine carbamate tetramer with Z-stilbene linker (Z-NCTS). Binding of Z-NCTS could induce the formation of an active folding structure and therebyr estore ribozyme activity,w here Z-NCTS acts as amolecular glue to bring two isolated RNAloops into contact with each other.N ext, we designed aZ -NCTS-responsive genetic switch using the HHR sequence inserted into the 3' untranslated region as ac is-acting element. We demonstrated that the rationally designed ribozyme switch enabled regulation of gene expression by Z-NCTS and was functional in mammalian cells.

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Modulation of the E. coli rpoH Temperature Sensor with Triptycene‐Based Small Molecules

2016

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Regulation of the heat shock response (HSR) is essential in all living systems. In E. coli, the HSR is regulated by the alternative σ factor, σ32, which is encoded by the rpoH gene. The mRNA of rpoH adopts a complex secondary structure critical for proper translation of the σ32 protein. At low temperature the rpoH gene transcript forms a highly structured mRNA containing several three-way junctions, including a rare perfectly paired three-way junction (3WJ). This complex secondary structure serves as a primitive but highly effective strategy for thermal control of gene expression. Here, we report the first small molecule modulators of the E. coli σ32 mRNA temperature sensor.

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A Synthetic Riboswitch that Operates using a Rationally Designed Ligand–RNA Pair

Cited by 5 publications

References 41 publications

Modulation of the E. coli rpoH Temperature Sensor with Triptycene‐Based Small Molecules

Modulation of the E. coli rpoH Temperature Sensor with Triptycene‐Based Small Molecules

Restoration of Ribozyme Tertiary Contact and Function by Using a Molecular Glue for RNA

Modulation of the E. coli rpoH Temperature Sensor with Triptycene‐Based Small Molecules

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