Recent advances in molecular machines based on toehold‐mediated strand displacement reaction

Guo, Yunchang; Bing, Wei; Xiao, Shiyan; Yao, Dongbao; Li, Hui; Xu, Huaguo; Song, Tingjie; Li, Xiang; Liang, Haojun

doi:10.1007/s40484-017-0097-2

Cited by 26 publications

(26 citation statements)

References 115 publications

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“…This type of strand exchange is initiated by a single-stranded oligomer (i.e., the invading strand) binding to an unpaired domain (the “toehold”) of a double-stranded duplex (for a review see ref. 61 ). The toehold can also originate in the loop of a hairpin 60 , as might be the case of BSL (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

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Structural basis of intron selection by U2 snRNP in the presence of covalent inhibitors

Cretu

Gee²,

Liu³

et al. 2021

Nat Commun

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Intron selection during the formation of prespliceosomes is a critical event in pre-mRNA splicing. Chemical modulation of intron selection has emerged as a route for cancer therapy. Splicing modulators alter the splicing patterns in cells by binding to the U2 snRNP (small nuclear ribonucleoprotein)—a complex chaperoning the selection of branch and 3′ splice sites. Here we report crystal structures of the SF3B module of the U2 snRNP in complex with spliceostatin and sudemycin FR901464 analogs, and the cryo-electron microscopy structure of a cross-exon prespliceosome-like complex arrested with spliceostatin A. The structures reveal how modulators inactivate the branch site in a sequence-dependent manner and stall an E-to-A prespliceosome intermediate by covalent coupling to a nucleophilic zinc finger belonging to the SF3B subunit PHF5A. These findings support a mechanism of intron recognition by the U2 snRNP as a toehold-mediated strand invasion and advance an unanticipated drug targeting concept.

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Section: Resultsmentioning

confidence: 99%

“…6). In this respect, the mechanism of BSL's unwinding with concomitant U2/intron pairing is reminiscent of a toehold-mediated strand invasion reaction [59][60][61] , where three exposed bases of BSL act as an internal toehold (Fig. 6a, b, d).…”

Section: Comparison Between Fr901464 and Pladienolide Analogsmentioning

confidence: 99%

Structural basis of intron selection by U2 snRNP in the presence of covalent inhibitors

Cretu

Gee²,

Liu³

et al. 2021

Nat Commun

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“…Detailed insight into biological building blocks and their assembly principles has inspired the field of nanotechnology; particular interest has been paid to DNA, in which specific molecular interactions can be easily encoded in a nucleotide sequence. − The major mechanism to achieve dynamic interactions in DNA-based systems is toehold-mediated strand displacement . A bimolecular association between a target and an incumbent strand is reversed by addition of an invader oligonucleotide, which displaces the incumbent (Figure ).…”

Section: Introductionmentioning

confidence: 99%

Modeling DNA-Strand Displacement Reactions in the Presence of Base-Pair Mismatches

2020

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Toehold-mediated strand displacement is the most abundantly used method to achieve dynamic switching in DNA-based nanotechnology. An 'invader' strand binds to the 'toehold' overhang of a target strand and replaces a targetbound 'incumbent' strand. Hereby, complementarity of the invader to the single-stranded toehold provides the energetic bias of the reaction. Despite the widespread use of strand displacement reactions for realizing dynamic DNA nanostructures, variants on the basic motif have not been completely characterized. Here we introduce a simple thermodynamic model, which is capable of quantitatively describing the kinetics of strand displacement reactions in the presence of mismatches, using a minimal set of parameters. Furthermore, our model highlights that base pair fraying and internal loop formation are important mechanisms when involving mismatches in the displacement process. Our model should provide a helpful tool for the rational design of strand-displacement reaction networks.

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“…HCR was firstly proposed by Dirk et al in 2004 [1], and later on, applied to various detection targets [2,3]. The HCR is, in essence, a type of room temperature isothermal DNA chain amplification method.…”

Section: Introductionmentioning

confidence: 99%

Hybridization Chain Reactions Targeting the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Chang

Yang

et al. 2020

IJMS

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In this work, hybridization chain reactions (HCRs) toward Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) nucleocapsid phosphoproteins gene loci and human RNase P are proposed to provide an isothermal amplification screening tool. The proposed chain reactions target the complementary DNA (cDNA) of SARS-CoV-2, with loci corresponding to gold-standard polymerase chain reaction (PCR) loci. Four hybridization chain reaction reactions are demonstrated herein, targeting N1/N2/N3 loci and human RNase P. The design of the hybridization chain reaction, herein, is assisted with an algorithm. The algorithm helps to search target sequences with low local secondary structure and high hybridization efficiency. The loop domain of the fuel hairpin molecule H1 and H2, which are the tunable segments in such reactions, are used as an optimization parameter to improve the hybridization efficiency of the chain reaction. The algorithm-derived HCR reactions were validated with gel electrophoresis. All proposed reactions exhibit a hybridization complex with a molecular mass >1.5k base pairs, which is clear evidence of chain reaction. The hybridization efficiency trend revealed by gel electrophoresis corresponds nicely to the simulated data from the algorithm. The HCR reactions and the corresponding algorithm serve as a basis to further SARS-CoV-2 sensing applications and facilitate better screening strategies for the prevention of on-going pandemics.

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Recent advances in molecular machines based on toehold‐mediated strand displacement reaction

Cited by 26 publications

References 115 publications

Structural basis of intron selection by U2 snRNP in the presence of covalent inhibitors

Structural basis of intron selection by U2 snRNP in the presence of covalent inhibitors

Modeling DNA-Strand Displacement Reactions in the Presence of Base-Pair Mismatches

Hybridization Chain Reactions Targeting the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

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