A general approach to the design of allosteric, transcription factor-regulated DNAzymes
Open accessAbstract
Here we explore a general strategy for the rational design of nucleic acid catalysts that can be allosterically activated by specific nucleic-acid binding proteins. To demonstrate this we have combined a catalytic DNAzyme sequence and the consensus sequence recognized by specific transcription factors to create a construct exhibiting two low-energy conformations: a more stable conformation lacking catalytic activity and lacking the transcription factor binding site, and a less stable conformation that is both catalytically active and competent to bind the transcription factor. The presence of the target transcription factor pushes the equilibrium between these states towards the latter conformation, concomitantly activating catalysis. To demonstrate this we have designed and characterized two peroxidase-like DNAzymes whose activities are triggered upon binding either TATA binding protein or the microphthalmia-associated transcription factor. Our approach augments the current tool kit for the allosteric control of DNAzymes and ribozymes and, because transcription factors control many key biological functions, could have important clinical and diagnostic applications.
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The presence of the transcription factor pushes the equilibrium between these states toward the catalytically active one.
“The presence of the transcription factor pushes the equilibrium between these states toward the catalytically active one, in a manner that can be finely controlled further by optimizing the original design (Adornetto et al., 2015).”
From Allostery in Its Many Disguises: From Theory to Applications (2019) · cites this paper as Adornetto et al., 2015
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Mfold web server for nucleic acid folding and hybridization prediction
Zuker, M. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg595 · Cited by 13,404 · see citing works
Breaker, R. R., & Joyce, G. F. (1994) · Chemistry & Biology · doi:10.1016/1074-5521(94)90014-0 · Cited by 1,479 · see citing works
Synthetic biology: applications come of age
Khalil, A. S., & Collins, J. J. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2775 · Cited by 1,385 · see citing works
DNA-enhanced peroxidase activity of a DNA aptamer-hemin complex
Travascio, P., Li, Y., & Sen, D. (1998) · Chemistry & Biology · doi:10.1016/s1074-5521(98)90006-0 · Cited by 1,007 · see citing works
Functional Aptamers and Aptazymes in Biotechnology, Diagnostics, and Therapy
Famulok, M., Hartig, J. S., & Mayer, G. (2007) · Chemical Reviews · doi:10.1021/cr0306743 · Cited by 889 · see citing works
Toehold Switches: De-Novo-Designed Regulators of Gene Expression
Green, A. A., Silver, P. A., Collins, J. J., & Yin, P. (2014) · Cell · doi:10.1016/j.cell.2014.10.002 · Cited by 817 · see citing works
DNAzymes for sensing, nanobiotechnology and logic gate applications
Willner, I., Shlyahovsky, B., Zayats, M., & Willner, B. (2008) · Chemical Society Reviews · doi:10.1039/b718428j · Cited by 791 · see citing works
Structure and evolution of transcriptional regulatory networks
Babu, M. M., Luscombe, N. M., Aravind, L., Gerstein, M., & Teichmann, S. A. (2004) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2004.05.004 · Cited by 764 · see citing works
Self-Sustained Replication of an RNA Enzyme
Lincoln, T. A., & Joyce, G. F. (2009) · Science · doi:10.1126/science.1167856 · Cited by 670 · see citing works
Liu, J., & Lu, Y. (2007) · Journal of the American Chemical Society · doi:10.1021/ja0717358 · Cited by 647 · see citing works
TBP, a universal eukaryotic transcription factor?Preprint
Hernandez, N. (1993) · Genes & Development · doi:10.1101/gad.7.7b.1291 · Cited by 568 · see citing works
A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma
Bertolotto, C., Lesueur, F., Giuliano, S., Strub, T., de Lichy, M., Bille, K., Dessen, P., d’Hayer, B., Mohamdi, H., Remenieras, A., et al. (2011) · Nature · doi:10.1038/nature10539 · Cited by 526 · see citing works
Liu, J., Brown, A. K., Meng, X., Cropek, D. M., Istok, J. D., Watson, D. B., & Lu, Y. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0607875104 · Cited by 523 · see citing works
Mechanisms of cooperativity and allosteric regulation in proteins
Perutz, M. F. (1990) · Comparative Biochemistry and Physiology Part A Physiology · doi:10.1016/0300-9629(90)90139-j · Cited by 508 · see citing works
Catalytic Beacons for the Detection of DNA and Telomerase Activity
Xiao, Y., Pavlov, V. V., Niazov, T., Dishon, A., Kotler, M., & Willner, I. (2004) · Journal of the American Chemical Society · doi:10.1021/ja031875r · Cited by 407 · see citing works
“Transcription physiology” of pigment formation in melanocytes: central role of MITF
Vachtenheim, J., & Borovanský, J. (2010) · Experimental Dermatology · doi:10.1111/j.1600-0625.2009.01053.x · Cited by 399 · see citing works
Rational design of allosteric ribozymes
Tang, J. Y., & Breaker, R. R. (1997) · Chemistry & Biology · doi:10.1016/s1074-5521(97)90197-6 · Cited by 383 · see citing works
Catalytic Beacons for the Detection of DNA and Telomerase Activity
Xiao, Y., Pavlov, V. V., Niazov, T., Dishon, A., Kotler, M., & Willner, I. (2006) · Springer eBooks · doi:10.1007/1-4020-3384-2_15 · Cited by 376 · see citing works
The hammerhead, hairpin and VS ribozymes are catalytically proficient in monovalent cations alone
Murray, J. B., Seyhan, A. A., Walter, N. G., Burke, J. M., & Scott, W. G. (1998) · Chemistry & Biology · doi:10.1016/s1074-5521(98)90116-8 · Cited by 374 · see citing works
Pavlov, V. V., Xiao, Y., Gill, R., Dishon, A., Kotler, M., & Willner, I. (2004) · Analytical Chemistry · doi:10.1021/ac035219l · Cited by 351 · see citing works
Travascio, P., Witting, P. K., Mauk, A. G., & Sen, D. (2001) · Journal of the American Chemical Society · doi:10.1021/ja0023534 · Cited by 351 · see citing works
Aminoacyl-RNA Synthesis Catalyzed by an RNA
Illangasekare, M., Sánchez, G., Nickles, T., & Yarus, M. (1995) · Science · doi:10.1126/science.7530860 · Cited by 347 · see citing works
A Synthetic Biology Framework for Programming Eukaryotic Transcription Functions
Khalil, A. S., Lu, T. K., Bashor, C. J., Ramirez, C. L., Pyenson, N. C., Joung, J. K., & Collins, J. J. (2012) · Cell · doi:10.1016/j.cell.2012.05.045 · Cited by 328 · see citing works
Liu, X., Freeman, R., Golub, E., et al. (2011) · ACS Nano · doi:10.1021/nn202799d · Cited by 274 · see citing works
Engineered allosteric ribozymes as biosensor components
Breaker, R. R. (2002) · Current Opinion in Biotechnology · doi:10.1016/s0958-1669(02)00281-1 · Cited by 266 · see citing works
Aksan, I., & Goding, C. R. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.12.6930 · Cited by 205 · see citing works
Aptamer−DNAzyme Hairpins for Amplified Biosensing
Teller, C., Shimron, S., & Willner, I. (2009) · Analytical Chemistry · doi:10.1021/ac901773b · Cited by 199 · see citing works
Improved Aptazyme Design and In Vivo Screening Enable Riboswitching in Bacteria
Wieland, M., & Hartig, J. S. (2008) · Angewandte Chemie International Edition · doi:10.1002/anie.200703700 · Cited by 184 · see citing works
Aptamers for allosteric regulation
Vinkenborg, J. L., Karnowski, N., & Famulok, M. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.609 · Cited by 183 · see citing works
Vallée‐Bélisle, A., Ricci, F., & Plaxco, K. W. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904005106 · Cited by 177 · see citing works
Self-citationProtein-dependent ribozymes report molecular interactions in real time
Hartig, J. S., Najafi-Shoushtari, S. H., Grüne, I., Yan, A. C., Ellington, A. D., & Famulok, M. (2002) · Nature Biotechnology · doi:10.1038/nbt0702-717 · Cited by 148 · see citing works
Deoxyribozymes: new activities and new applications
Emilsson, G. M., & Breaker, R. R. (2002) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-002-8452-4 · Cited by 147 · see citing works
DNAzyme technology and cancer therapy: cleave and let die
Dass, C. R., Choong, P., & Khachigian, L. M. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-07-0510 · Cited by 145 · see citing works
G-quadruplex-based DNAzyme for facile colorimetric detection of thrombin
Li, T., Wang, E., & Dong, S. (2008) · Chemical Communications · doi:10.1039/b805565c · Cited by 144 · see citing works
Allosteric nucleic acid catalysts
Soukup, G. A., & Breaker, R. R. (2000) · Current Opinion in Structural Biology · doi:10.1016/s0959-440x(00)00090-7 · Cited by 123 · see citing works
Inventing and improving ribozyme function: Rational design versus iterative selection methods
Breaker, R. R., & Joyce, G. F. (1994) · Trends in biotechnology · doi:10.1016/0167-7799(94)90138-4 · Cited by 118 · see citing works
The effect of cytidine on the structure and function of an RNA ligase ribozyme
Rogers, J., & Joyce, G. F. (2001) · RNA · doi:10.1017/s135583820100228x · Cited by 118 · see citing works
Structural diversity of self-cleaving ribozymes
Tang, J. Y., & Breaker, R. R. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.11.5784 · Cited by 113 · see citing works
Artificial riboswitches for gene expression and replication control of DNA and RNA viruses
Ketzer, P., Kaufmann, J. K., Engelhardt, S., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1318563111 · Cited by 113 · see citing works
Logic Gates and Antisense DNA Devices Operating on a Translator Nucleic Acid Scaffold
Shlyahovsky, B., Li, Y., Lioubashevski, O., et al. (2009) · ACS Nano · doi:10.1021/nn900085x · Cited by 111 · see citing works
A tiny RNA that catalyzes both aminoacyl-RNA and peptidyl-RNA synthesis
Illangasekare, M., & Yarus, M. (1999) · RNA · doi:10.1017/s1355838299991264 · Cited by 104 · see citing works
A novel ribozyme with ester transferase activity
Jenne, A., & Famulok, M. (1998) · Chemistry & Biology · doi:10.1016/s1074-5521(98)90084-9 · Cited by 97 · see citing works
A general design strategy for protein-responsive riboswitches in mammalian cells
Ausländer, S., Stücheli, P., Rehm, C., Ausländer, D., Hartig, J. S., & Fussenegger, M. (2014) · Nature Methods · doi:10.1038/nmeth.3136 · Cited by 96 · see citing works
Transcription Factor Beacons for the Quantitative Detection of DNA Binding Activity
Vallée‐Bélisle, A., Bonham, A. J., Reich, N. O., Ricci, F., & Plaxco, K. W. (2011) · Journal of the American Chemical Society · doi:10.1021/ja204775k · Cited by 87 · see citing works
Self-citationA General Strategy for Effector-mediated Control of RNA-cleaving Ribozymes and DNA Enzymes
Wang, D. Y., Lai, B. H. Y., & Sen, D. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00046-3 · Cited by 87 · see citing works
DNAzyme-based 2:1 and 4:1 multiplexers and 1:2 demultiplexer
Orbach, R., Remacle, F., Levine, R. D., et al. (2013) · Chemical Science · doi:10.1039/c3sc52752b · Cited by 82 · see citing works
ATP-Dependent Allosteric DNA Enzymes
Levy, M., & Ellington, A. D. (2002) · Chemistry & Biology · doi:10.1016/s1074-5521(02)00123-0 · Cited by 82 · see citing works
Klauser, B., Atanasov, J., Siewert, L. K., & Hartig, J. S. (2014) · ACS Synthetic Biology · doi:10.1021/sb500062p · Cited by 81 · see citing works
A full-adder based on reconfigurable DNA-hairpin inputs and DNAzyme computing modules
Orbach, R., Wang, F., Lioubashevski, O., et al. (2014) · Chemical Science · doi:10.1039/c4sc00914b · Cited by 81 · see citing works
Wang, D. Y. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.8.1735 · Cited by 78 · see citing works
Detection of Metal Ions (Cu2+, Hg2+) and Cocaine by Using Ligation DNAzyme Machinery
Wang, F., Orbach, R., & Willner, I. (2012) · Chemistry - A European Journal · doi:10.1002/chem.201201479 · Cited by 67 · see citing works
Autocatalytic aptazymes enable ligand-dependent exponential amplification of RNA
Lam, B. J., & Joyce, G. F. (2009) · Nature Biotechnology · doi:10.1038/nbt.1528 · Cited by 62 · see citing works
The Stability of the TFIIA-TBP-DNA Complex Is Dependent on the Sequence of the TATAAA Element
Stewart, J. J., & Stargell, L. A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105276200 · Cited by 59 · see citing works
Wang, D. Y., & Sen, D. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.4811 · Cited by 56 · see citing works
Bareket‐Samish, A., Cohen, I., & Haran, T. E. (2000) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.3797 · Cited by 55 · see citing works
Khan, A. U. (2006) · Clinica Chimica Acta · doi:10.1016/j.cca.2005.11.023 · Cited by 54 · see citing works
Ion‐Responsive Hemin–G‐Quadruplexes for Switchable DNAzyme and Enzyme Functions
Aleman‐Garcia, M. A., Orbach, R., & Willner, I. (2014) · Chemistry - A European Journal · doi:10.1002/chem.201304702 · Cited by 54 · see citing works
Chiuman, W., & Li, Y. (2007) · PLoS ONE · doi:10.1371/journal.pone.0001224 · Cited by 49 · see citing works
Beyond allostery: Catalytic regulation of a deoxyribozyme through an entropy-driven DNA amplifier
Eckhoff, G., Codrea, V., Ellington, A. D., & Chen, X. (2010) · Journal of Systems Chemistry · doi:10.1186/1759-2208-1-13 · Cited by 42 · see citing works
DNAzymes as potential therapeutic molecules.
Isaka, Y. (2007) · PubMed · Cited by 36 · see citing works
Effects of DNAzymes targeting Aurora kinase A on the growth of human prostate cancer
Qu, Y., Zhang, L., Mao, M., et al. (2008) · Cancer Gene Therapy · doi:10.1038/cgt.2008.22 · Cited by 27 · see citing works
Lam, B. J., & Joyce, G. F. (2011) · Journal of the American Chemical Society · doi:10.1021/ja111136d · Cited by 25 · see citing works
Mechanisms of cooperativity and allosteric regulation in proteins
Semenza, G. (1991) · FEBS Letters · doi:10.1016/0014-5793(91)80424-2 · Cited by 23 · see citing works
Balke, D., Wichert, C., Appel, B., & Müller, S. (2014) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-014-5528-7 · Cited by 13 · see citing works
Fishful thinking: the rise and fall of MITF in melanoma
Goding, C. R. (2013) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12177 · Cited by 10 · see citing works
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Allostery in Its Many Disguises: From Theory to Applications
Wodak, S. J., Paci, E., Dokholyan, N. V., Berezovsky, I. N., Horovitz, A., Li, J., Hilser, V. J., Bahar, I., Karanicolas, J., Stock, G., et al. (2019) · Structure · doi:10.1016/j.str.2019.01.003 · Cited by 404 · see citing works
- Authors
- Adornetto, G., Porchetta, A., Palleschi, G., Plaxco, K. W., & Ricci, F.
- Affiliations
- University of Rome Tor Vergata (IT)
- University of California, Santa Barbara (US)
- Corresponding author
- Ricci, F.
- Venue
- Chemical Science
- Publisher
- Royal Society of Chemistry (RSC)
- Published
- 2015
- Volume
- 6
- Issue
- 7
- Pages
- 3692-3696
- ISSN
- 2041-6520 (ISSN-L)
- 2041-6539
- PMC
- PMC5496187
- OpenAlex
- W2165808891
- Cited by
- 31
- References
- 65
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 7 · 2017: 2 · 2016: 2 · 2015: 2
- FWCI
- 1.88
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Chemical Science (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, cc-by)
- Funders
- European Research Council (336493)
- Research Executive Agency (Marie Curie IRSES)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- transcription factor regulation, TATA-binding protein, microphthalmia-associated transcription factor, allosteric activation, conformational equilibrium, transcription factor binding sites, ribozymes
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