Rational selection of small molecules that increase transcription through the GAA repeats found in Friedreich's ataxia
Open accessAbstract
Friedreich's ataxia (FRDA) is an autosomal recessive trinucleotide repeat disease with no effective therapy. Expanded GAA repeats in the first intron of the FRDA gene are thought to form unusual non‐B DNA conformations that decrease transcription and subsequently reduce levels of the encoded protein, frataxin. Frataxin plays a crucial role in iron metabolism and detoxification. To discover small molecules that increase transcription through the GAA repeat region in FRDA, we have made stable cell lines containing a portion of expanded intron 1 fused to a GFP reporter. Small molecules identified using the competition dialysis method were found to increase FRDA‐intron 1‐reporter gene expression. One of these compounds, pentamidine, increases frataxin levels in patient cells. Thus our approach can be used to detect small molecules of potential therapeutic value in FRDA.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
IRP binding to an IRE in the 5′ UTR blocks the assembly of the 43S translation preinitiation complex.
“IRP binding to an IRE in the 5′ UTR blocks the assembly of the 43S translation preinitiation complex (112).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [112]
Cites
Friedreich's Ataxia: Autosomal Recessive Disease Caused by an Intronic GAA Triplet Repeat Expansion
Campuzano, V., Montermini, L., Moltò, M. D., Pianese, L., Cossée, M., Cavalcanti, F., Monros, E., Rodius, F., Duclos, F., Monticelli, A., et al. (1996) · Science · doi:10.1126/science.271.5254.1423 · Cited by 2,786 · see citing works
CLASSIFICATION OF THE HEREDITARY ATAXIAS AND PARAPLEGIAS
Harding, A. E. B. (1983) · The Lancet · doi:10.1016/s0140-6736(83)92879-9 · Cited by 970 · see citing works
Diseases of Unstable Repeat Expansion: Mechanisms and Common Principles
Gatchel, J. R., & Zoghbi, H. Y. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1691 · Cited by 784 · see citing works
Frataxin is Reduced in Friedreich Ataxia Patients and is Associated with Mitochondrial Membranes
Campuzano, V., Montermini, L., Lutz, Y., Cova, L., Hindelang, C., Jiralerspong, S., Trottier, Y., Kish, S. J., Faucheux, B. A., Trouillas, P., et al. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.11.1771 · Cited by 739 · see citing works
Sequence and Structural Selectivity of Nucleic Acid Binding Ligands
Ren, J., & Chaires, J. B. (1999) · Biochemistry · doi:10.1021/bi992070s · Cited by 566 · see citing works
Self-citationBinding of Hoechst 33258 to the minor groove of B-DNA
Pjura, P. E., Grześkowiak, K., & Dickerson, R. E. (1987) · Journal of Molecular Biology · doi:10.1016/0022-2836(87)90123-9 · Cited by 531 · see citing works
DNA minor-groove recognition by small molecules (up to 2000)
Neidle, S. (2001) · Natural Product Reports · doi:10.1039/a705982e · Cited by 494 · see citing works
Current Protocols in Nucleic Acid Chemistry
(2001) · John Wiley & Sons, Inc. eBooks · doi:10.1002/0471142700 · Cited by 472 · see citing works
Friedreich ataxia: an overview
Delatycki, M. B., Williamson, R., & Forrest, S. M. (2000) · Journal of Medical Genetics · doi:10.1136/jmg.37.1.1 · Cited by 358 · see citing works
Oldfield, M. (1951) · The Lancet · doi:10.1016/s0140-6736(51)92659-1 · Cited by 345 · see citing works
Ohshima, K., Montermini, L., Wells, R. D., & Pandolfo, M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.23.14588 · Cited by 302 · see citing works
SMN-mediated assembly of RNPs: a complex story
Meister, G. (2002) · Trends in Cell Biology · doi:10.1016/s0962-8924(02)02371-1 · Cited by 235 · see citing works
Idebenone treatment in Friedreich patients: One-year-long randomized placebo-controlled trial
Mariotti, C., Solari, A., Torta, D., Marano, L., Fiorentini, C., & Donato, S. D. (2003) · Neurology · doi:10.1212/01.wnl.0000055872.50364.fc · Cited by 235 · see citing works
Friedreich ataxia: the oxidative stress paradox
Seznec, H., Simon, D., Bouton, C., Reutenauer, L., Hertzog, A., Golik, P., Procaccio, V., Patel, M., Drapier, J.-C., Koenig, M., et al. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi042 · Cited by 219 · see citing works
Advances in mechanisms of genetic instability related to hereditary neurological diseases
Wells, R. D. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki697 · Cited by 206 · see citing works
Gakh, O., Park, S., Liu, G., Macomber, L., Imlay, J. A., Ferreira, G. C., & Isaya, G. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddi461 · Cited by 184 · see citing works
Self-association of Coilin Reveals a Common Theme in Nuclear Body Localization
Hebert, M. D., & Matera, A. G. (2000) · Molecular Biology of the Cell · doi:10.1091/mbc.11.12.4159 · Cited by 180 · see citing works
Self-citationSeznec, H. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh114 · Cited by 138 · see citing works
Burnett, R., Melander, C., Puckett, J. W., Son, L. S., Wells, R. D., Dervan, P. B., & Gottesfeld, J. M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604939103 · Cited by 136 · see citing works
Searle, M. S., & Embrey, K. J. (1990) · Nucleic Acids Research · doi:10.1093/nar/18.13.3753 · Cited by 108 · see citing works
Recombinant human erythropoietin: effects on frataxin expression in vitro
Sturm, B., Stupphann, D., Kaun, C., Boesch, S., Schranzhofer, M., Wojta, J., Goldenberg, H., & Scheiber‐Mojdehkar, B. (2005) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2005.01568.x · Cited by 103 · see citing works
Pianese, L. (2004) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2003.028605 · Cited by 82 · see citing works
Interactions between Coilin and PIASy partially link Cajal bodies to PML bodies
Sun, J., Xu, H., Subramony, S. H., & Hebert, M. D. (2005) · Journal of Cell Science · doi:10.1242/jcs.02613 · Cited by 56 · see citing works
Self-citationChaires, J. B. (2005) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/1568011054222292 · Cited by 54 · see citing works
Self-citationSpecific binding of Hoechst 33258 to site 1 thymidylate synthase mRNA
Cho, J. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.10.2158 · Cited by 47 · see citing works
Idebenone treatment in Friedreich patients: One-year-long randomized placebo-controlled trial
Rustin, P., Bonnet, D., Rötig, A., Münnich, A., & Sidi, D. (2004) · Neurology · doi:10.1212/wnl.62.3.524 · Cited by 35 · see citing works
Frataxin and frataxin deficiency in Friedreich's ataxia
Wilson, R. B. (2003) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(02)00432-x · Cited by 32 · see citing works
Rustin, P., Bonnet, D., Rötig, A., Münnich, A., Sidi, D., Mariotti, C., Taroni, F., Donato, S. D., Filla, A., & Moss, A. J. (2004) · Cited by 22 · see citing works
Therapeutic strategies in Friedreich’s ataxia
Schöls, L. J., Meyer, C., Schmid, G., Wilhelms, I., & Przuntek, H. (2004) · Journal of neural transmission. Supplementum · doi:10.1007/978-3-7091-0579-5_16 · Cited by 21 · see citing works
A Competition Dialysis Assay for the Study of Structure‐Selective Ligand Binding to Nucleic Acids
Chaires, J. B. (2002) · Current Protocols in Nucleic Acid Chemistry · doi:10.1002/0471142700.nc0803s11 · Cited by 20 · see citing works
Self-citationDisney, M. D., Stephenson, R., Wright, T. W., Haidaris, C. G., Turner, D. H., & Gigliotti, F. (2005) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.49.4.1326-1330.2005 · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Intracellular iron transport and storage: from molecular mechanisms to health implications
Mackenzie, E. L., Iwasaki, K., & Tsuji, Y. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1893 · Cited by 526 · see citing works
Friedreich Ataxia: Molecular Mechanisms, Redox Considerations, and Therapeutic Opportunities
Santos, R., Lefevre, S. D., Sliwa, D., Seguin, A., Camadro, J., & Lesuisse, E. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.3015 · Cited by 191 · see citing works
A rapid, noninvasive immunoassay for frataxin: Utility in assessment of Friedreich ataxia
Deutsch, E. C., Santani, A., Perlman, S., Farmer, J. M., Stolle, C. A., Marusich, M. F., & Lynch, D. R. (2010) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2010.07.001 · Cited by 104 · see citing works
Excision of Expanded GAA Repeats Alleviates the Molecular Phenotype of Friedreich's Ataxia
Li, Y., Polak, U., Bhalla, A. D., Rozwadowska, N., Napierala, J. S., Lynch, D. R., Dent, S., & Напиерала, М. (2015) · Molecular Therapy · doi:10.1038/mt.2015.41 · Cited by 97 · see citing works
Reducing Levels of Toxic RNA with Small Molecules
Coonrod, L. A., Nakamori, M., Wang, W., Carrell, S., Hilton, C. L., Bodner, M. J., Siboni, R. B., Docter, A. G., Haley, M. M., Thornton, C. A., et al. (2013) · ACS Chemical Biology · doi:10.1021/cb400431f · Cited by 87 · see citing works
Advancements in the pathophysiology of Friedreich’s Ataxia and new prospects for treatments
Babady, N. E., Carelle, N., Wells, R. D., Rouault, T. A., Hirano, M., Lynch, D. R., Delatycki, M. B., Wilson, R. B., Isaya, G., & Puccio, H. (2007) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2007.05.009 · Cited by 73 · see citing works
Martelli, A., Напиерала, М., & Puccio, H. M. (2012) · Disease Models & Mechanisms · doi:10.1242/dmm.008706 · Cited by 73 · see citing works
Soragni, E., Herman, D., Dent, S., Gottesfeld, J. M., Wells, R. D., & Напиерала, М. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn604 · Cited by 73 · see citing works
Li, Y., Lu, Y., Polak, U., Lin, K., Shen, J., Farmer, J. M., Seyer, L. A., Bhalla, A. D., Rozwadowska, N., Lynch, D. R., et al. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv397 · Cited by 70 · see citing works
Small molecules affecting transcription in Friedreich ataxia
Gottesfeld, J. M. (2007) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2007.06.014 · Cited by 67 · see citing works
Lateral-flow immunoassay for the frataxin protein in Friedreich’s ataxia patients and carriers
Willis, J. H., Isaya, G., Gakh, O., Capaldi, R., & Marusich, M. F. (2008) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2008.03.019 · Cited by 58 · see citing works
DNA triplex structures in neurodegenerative disorder, Friedreich’s ataxia
Rajeswari, M. R. (2012) · Journal of Biosciences · doi:10.1007/s12038-012-9219-1 · Cited by 47 · see citing works
Modulation of DNA structure formation using small molecules
del Mundo, I. M. A., Vásquez, K. M., & Wang, G. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2019.118539 · Cited by 45 · see citing works
New insights into repeat instability
McIvor, E., Polak, U., & Напиерала, М. (2010) · RNA Biology · doi:10.4161/rna.7.5.12745 · Cited by 44 · see citing works
Flavin Adenine Dinucleotide Rescues the Phenotype of Frataxin Deficiency
González‐Cabo, P., Ros, S., & Palau, F. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008872 · Cited by 37 · see citing works
Sandi, C., Sandi, M., Jassal, H., Ezzatizadeh, V., Anjomani‐Virmouni, S., Al‐Mahdawi, S., & Pook, M. A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0089488 · Cited by 34 · see citing works
Pharmacotherapy for Friedreich Ataxia
Tsou, A. Y., Friedman, L. S., Wilson, R. B., & Lynch, D. R. (2009) · CNS Drugs · doi:10.2165/00023210-200923030-00003 · Cited by 30 · see citing works
A high throughput electrochemiluminescence assay for the quantification of frataxin protein levels
Steinkellner, H., Scheiber‐Mojdehkar, B., Goldenberg, H., & Sturm, B. (2009) · Analytica Chimica Acta · doi:10.1016/j.aca.2009.11.036 · Cited by 30 · see citing works
Verma, A. K., Khan, E., Bhagwat, S. R., & Kumar, A. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-01724-4 · Cited by 27 · see citing works
Current and emerging treatment options in the management of Friedreich ataxia
Mancuso, M. (2010) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s6916 · Cited by 26 · see citing works
Lufino, M. M., Silva, A. M., Nemeth, A. H., Alegre‐Abarrategui, J., Russell, A. J., & Wade‐Martins, R. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt370 · Cited by 22 · see citing works
Replication dependent and independent mechanisms of GAA repeat instability
Masnovo, C., Lobo, A. F., & Mirkin, S. M. (2022) · DNA repair · doi:10.1016/j.dnarep.2022.103385 · Cited by 21 · see citing works
Li, J., Begbie, A. J., Boehm, B. J., Button, A. L., Whidborne, C., Pouferis, Y., Huang, D. M., & Pukala, T. L. (2018) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-018-2077-9 · Cited by 21 · see citing works
Identification of Trinucleotide Repeat Ligands with a FRET Melting Assay
Amrane, S., Cian, A. D., Rosu, F., Kaiser, M., Pauw, E. D., Teulade‐Fichou, M., & Mergny, J. (2008) · ChemBioChem · doi:10.1002/cbic.200800062 · Cited by 20 · see citing works
Bergquist, H., Nikravesh, A., Fernández, R. D., Larsson, V. J., Nguyen, C.-H., Good, L., & Zain, R. (2009) · ChemBioChem · doi:10.1002/cbic.200900263 · Cited by 19 · see citing works
Friedreich Ataxia: An Update on Animal Models, Frataxin Function and Therapies
González‐Cabo, P., Llorens, J. V., Palau, F., & Moltó, M. D. (2009) · Advances in experimental medicine and biology · doi:10.1007/978-90-481-2813-6_17 · Cited by 18 · see citing works
Bergquist, H., Rocha, C. S. J., Álvarez-Asencio, R., Nguyen, C.-H., Rutland, M. W., Smith, C. I. E., Good, L., Nielsen, P. E., & Zain, R. (2016) · PLoS ONE · doi:10.1371/journal.pone.0165788 · Cited by 17 · see citing works
Targeting the gene in Friedreich ataxia
Hebert, M. D. (2008) · Biochimie · doi:10.1016/j.biochi.2007.12.005 · Cited by 16 · see citing works
Self-citationLi, A., Bouhss, A., Clément, M., Bauvais, C., Taylor, J. P., Bollot, G., & Pastré, D. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1298441 · Cited by 15 · see citing works
Gene-based approaches toward Friedreich ataxia therapeutics
Hebert, M. D., & Whittom, A. A. (2007) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-7293-6 · Cited by 14 · see citing works
Self-citationMicroscopic Rearrangement of Bound Minor Groove Binders Detected by NMR
Rettig, M., Germann, M. W., Ismail, M. A., Batista-Parra, A., Munde, M. M., Boykin, D. W., & Wilson, W. D. (2012) · The Journal of Physical Chemistry B · doi:10.1021/jp301143e · Cited by 13 · see citing works
Schreiber, A. M., Li, Y., Chen, Y., Napierala, J. S., & Напиерала, М. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.836476 · Cited by 9 · see citing works
Novel Therapeutic Challenges in Cerebellar Diseases
Matilla‐Dueñas, A., Infante, J., Serrano, C., Ivánovic-Barbeito, Y., Álvarez, R., & Sánchez, I. (2012) · Springer eBooks · doi:10.1007/978-3-030-23810-0_106 · Cited by 9 · see citing works
Disorders of the Cerebellum, Including the Degenerative Ataxias
Subramony, S. H. (2008) · Elsevier eBooks · doi:10.1016/b978-0-7506-7525-3.50114-x · Cited by 4 · see citing works
Self-citationVillaseñor, R., Miraglia, L. J., Romero, A., Tu, B. P., Punga, T., Knuckles, P., Duss, S., Orth, T., & Bühler, M. (2015) · SLAS DISCOVERY · doi:10.1177/1087057114568071
The effect of nucleic acid-binding ligands on CTG/CAG repeat DNA metabolism in vitro
Chiang, K. (2018) · TSpace (University of Toronto)
- Authors
- Grant, L., Sun, J., Xu, H., Subramony, S. H., Chaires, J. B., & Hebert, M. D.
- Affiliations
- University of Mississippi Medical Center (US)
- University of Louisville (US)
- Corresponding author
- Hebert, Michael D.
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2006-09-15
- Volume
- 580
- Issue
- 22
- Pages
- 5399-5405
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- PMC
- PMC1847611
- OpenAlex
- W2055007938
- Cited by
- 36
- References
- 31
- Citations by year
- 2023: 1 · 2022: 2 · 2019: 2 · 2018: 2 · 2016: 1 · 2015: 3 · 2014: 1 · 2013: 2 · 2012: 4
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Friedreich's Ataxia Research Alliance
- National Institutes of Health
- National Cancer Institute (R01CA035635)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- Friedreich's ataxia, GAA repeat expansion, frataxin, transcriptional activation, small molecule screening, non-B DNA structures, intron 1, pentamidine, GFP reporter, iron metabolism
- MeSH terms
- Frataxin, Antifungal Agents, Cells, Cultured, Drug Evaluation, Preclinical, Friedreich Ataxia, Humans, Lymphocytes, Nucleic Acid Conformation, Pentamidine, Transcription, Genetic, Drug Design, Genes, Reporter, Trinucleotide Repeat Expansion, Iron-Binding Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
