Synthetic translational regulation by an L7Ae–kink-turn RNP switch

Saito, Hirohide; Kobayashi, Toshikatsu; Hara, Tomoaki; Fujita, Yoshihiko; Hayashi, Karin; Furushima, Rie; Inoue, Tan

doi:10.1038/nchembio.273

Cited by 152 publications

(140 citation statements)

References 46 publications

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“…Guided by crystal structures of L7Ae-RNA 22 and of myosin VI 23,24 , we aligned the terminal helices and optimized the phasing of the junction to orient a bound kink-turn motif as a structural foundation from which to build extended RNA lever arms. The interaction of L7Ae with kink-turn motifs has been previously exploited in nanotechnology and synthetic biology applications 25–27 , and yields stable complexes with reported K d values of ~1 nM and dissociation rates of ~2–7 × 10 −4 s −1 25,27,28 .…”

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confidence: 99%

Controllable molecular motors engineered from myosin and RNA

et al. 2017

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Engineering biomolecular motors can provide direct tests of structure-function relationships and customized components for controlling molecular transport in artificial systems1 or in living cells2. Previously, synthetic nucleic acid motors3–5 and modified natural protein motors6–10 have been developed in separate complementary strategies for achieving tunable and controllable motor function. Integrating protein and nucleic acid components to form engineered nucleoprotein motors may enable additional sophisticated functionalities. However, this potential has only begun to be explored in pioneering work harnessing DNA scaffolds to dictate the spacing, number, and composition of tethered protein motors11–15. Here, we describe myosin motors that incorporate RNA lever arms, forming hybrid assemblies in which conformational changes in the protein motor domain are amplified and redirected by nucleic acid structures. The RNA lever arm geometry determines the speed and direction of motor transport, and can be dynamically controlled using programmed transitions in lever arm structure7,9. We have characterized the hybrid motors using in vitro motility assays, single-molecule tracking, cryo-electron microscopy, and structural probing16. Our designs include nucleoprotein motors that reversibly change direction in response to oligonucleotides that drive strand-displacement17 reactions. In multimeric assemblies, the controllable motors walk processively along actin filaments at speeds of 10–20 nm s−1. Finally, to illustrate the potential for multiplexed addressable control, we demonstrate sequence-specific responses of RNA variants to oligonucleotide signals.

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confidence: 99%

Controllable molecular motors engineered from myosin and RNA

et al. 2017

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“…Design of riboswitches that bind protein ligands is another interesting direction. Saito et al constructed an L7Ae-kink-turn RNA-protein (RNP) switch, in which the small molecule-RNA interaction was replaced by protein-RNA interaction (Saito et al, 2010). The design of riboswitch to be controlled by protein ligand could greatly extend its applications in cellular context.…”

Section: Synthetic Rna Elements For Post-transcriptional Regulationmentioning

confidence: 99%

Synthetic circuits, devices and modules

Zhao

Jiang

2010

Protein Cell

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The aim of synthetic biology is to design artificial biological systems for novel applications. From an engineering perspective, construction of biological systems of defined functionality in a hierarchical way is fundamental to this emerging field. Here, we highlight some current advances on design of several basic building blocks in synthetic biology including the artificial gene control elements, synthetic circuits and their assemblies into devices and modules. Such engineered basic building blocks largely expand the synthetic toolbox and contribute to our understanding of the underlying design principles of living cells.

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“…Recently, control switches have been engineered to regulate the expression of genes into proteins; for example, RNAbinding proteins, like the archaeal ribosomal protein L7Ae, can be switched on by an input protein to block translation or by binding to an RNA motif integrated in the 5 0 UTR of an mRNA transcript [78,102]. An aptamer controlled by the Hoechst 33258 dye has also been shown to inhibit translation in the presence of Hoechst 33258, thus functioning as a translational switch [75].…”

Section: Translational Switches (Figure 2)mentioning

confidence: 99%

Mammalian synthetic biology: emerging medical applications

Kis

Pereira

Homma

et al. 2015

J. R. Soc. Interface.

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In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON-OFF switches, categorized into transcriptional, post-transcriptional, translational and posttranslational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes.

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Synthetic translational regulation by an L7Ae–kink-turn RNP switch

Cited by 152 publications

References 46 publications

Controllable molecular motors engineered from myosin and RNA

Controllable molecular motors engineered from myosin and RNA

Synthetic circuits, devices and modules

Mammalian synthetic biology: emerging medical applications

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