Single-molecule study of the CUG repeat-MBNL1 interaction and its inhibition by small molecules

Nucleic Acids Research

Volumn 41, Issue 13, 2013, Pages 6687-6697

  Jahromi, Amin Haghighat ^a,b   Honda, Masayoshi ^c   Zimmerman, Steven C ^a,b   Spies, Maria ^c  

^a UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

^b UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

^c UNIVERSITY OF IOWA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

9 [[4 [(4,6 DIAMINO 1,3,5 TRIAZIN 2 YL) AMINO] BUTYL] AMINO] N METHYLACRIDINE 2 CARBOXAMIDE; MUSCLE PROTEIN; MUSCLEBLIND LIKE 1 PROTEIN; N,N' [[PROPANE 1,3 DIYLBIS(AZANEDIYL)] BIS(PROPANE 3,1 DIYL)] BIS[9 [[4 ((4,6 DIAMINO 1,3,5 TRIAZIN 2 YL) AMINO) BUTYL] AMINO] ACRIDINE 4 CARBOXAMIDE]; PROTEIN INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; BINDING KINETICS; CUG REPEAT; DIMERIZATION; ENZYME INHIBITOR COMPLEX; FLUORESCENCE MICROSCOPY; LIGAND BINDING; MOLECULAR INTERACTION; MYOTONIC DYSTROPHY; PRIORITY JOURNAL; PROTEIN DNA BINDING; PROTEIN INTERACTION; PROTEIN STABILITY; SINGLE MOLECULE STUDY; TOTAL INTERNAL REFLECTION FLUORESCENCE MICROSCOPY; TRINUCLEOTIDE REPEAT;

DRUG EVALUATION, PRECLINICAL; LIGANDS; MICROSCOPY, FLUORESCENCE; RNA; RNA-BINDING PROTEINS; SMALL MOLECULE LIBRARIES; TRINUCLEOTIDE REPEATS;

EID: 84880523180     PISSN: 03051048     EISSN: 13624962     Source Type: Journal    
DOI: 10.1093/nar/gkt330     Document Type: Article

References (43)

1. Wheeler, T.M., Sobczak, K., Lueck, J.D., Osborne, R.J., Lin, X., Dirksen, R.T. and Thornton, C.A. (2009) Reversal of RNA dominance by displacement of protein sequestered on triplet repeat RNA. Science, 325, 336-339.
2. O'Rourke, J.R. and Swanson, M.S. (2009) Mechanisms of RNA-mediated disease. J. Biol. Chem., 284, 7419-7423.
3. Echeverria, G.V. and Cooper, T.A. (2012) RNA-binding proteins in microsatellite expansion disorders: mediators of RNA toxicity. Brain Res., 1462, 100-111.
4. Wheeler, T.M., Leger, A.J., Pandey, S.K., MacLeod, A.R., Nakamori, M., Cheng, S.H., Wentworth, B.M., Bennett, C.F. and Thornton, C.A. (2012) Targeting nuclear RNA for in vivo correction of myotonic dystrophy. Nature, 488, 111-115.
5. Garcia-Lopez, A., Llamusi, B., Orzaez, M., Perez-Paya, E. and Artero, R.D. (2011) In vivo discovery of a peptide that prevents CUG-RNA hairpin formation and reverses RNA toxicity in myotonic dystrophy models. Proc. Natl Acad. Sci. USA, 108, 11866-11871.
6. Foff, E.P. and Mahadevan, M.S. (2011) Therapeutics development in myotonic dystrophy type 1. Muscle Nerve, 44, 160-169.
7. Warf, M.B., Nakamori, M., Matthys, C.M., Thornton, C.A. and Berglund, J.A. (2009) Pentamidine reverses the splicing defects associated with myotonic dystrophy. Proc. Natl Acad. Sci. USA, 106, 18551-18556.
8. Ofori, L.O., Hoskins, J., Nakamori, M., Thornton, C.A. and Miller, B.L. (2012) From dynamic combinatorial 'hit' to lead: in vitro and in vivo activity of compounds targeting the pathogenic RNAs that cause myotonic dystrophy. Nucleic Acids Res., 40, 6380-6390.
9. Parkesh, R., Childs-Disney, J.L., Nakamori, M., Kumar, A., Wang, E., Wang, T., Hoskins, J., Tran, T., Housman, D., Thornton, C.A. et al. (2012) Design of a bioactive small molecule that targets the myotonic dystrophy type 1 RNA via an RNA motif-ligand database and chemical similarity searching. J. Am. Chem. Soc., 134, 4731-4742.
10. Pushechnikov, A., Lee, M.M., Childs-Disney, J.L., Sobczak, K., French, J.M., Thornton, C.A. and Disney, M.D. (2009) Rational design of ligands targeting triplet repeating transcripts that cause RNA dominant disease: application to myotonic muscular dystrophy type 1 and spinocerebellar ataxia type 3. J. Am. Chem. Soc., 131, 9767-9779.
11. Holdgate, G.A. and Gill, A.L. (2011) Kinetic efficiency: the missing metric for enhancing compound quality? Drug Discov. Today, 16, 910-913.
12. Blow, N. (2009) Proteins and proteomics: life on the surface. Nat. Methods, 6, 389-393.
13. Navratilova, I. and Myszka, D.G. (2006) Investigating biomolecular interactions and binding properties using SPR biosensors. Surf. Plasmon Reson. Based Sens., 4, 155-176.
14. Elenko, M.P., Szostak, J.W. and van Oijen, A.M. (2009) Singlemolecule imaging of an in vitro-evolved RNA aptamer reveals homogeneous ligand binding kinetics. J. Am. Chem. Soc., 131, 9866-9867.
15. Moffitt, J.R., Chemla, Y.R. and Bustamante, C. (2010) Methods in statistical kinetics. Methods Enzymol., 475, 221-257.
16. Karunatilaka, K.S., Solem, A., Pyle, A.M. and Rueda, D. (2010) Single-molecule analysis of Mss116-mediated group II intron folding. Nature, 467, 935-939.
17. Yuan, Y., Compton, S.A., Sobczak, K., Stenberg, M.G., Thornton, C.A., Griffith, J.D. and Swanson, M.S. (2007) Muscleblind-like 1 interacts with RNA hairpins in splicing target and pathogenic RNAs. Nucleic Acids Res., 35, 5474-5486. (Pubitemid 47423921)
18. Galletto, R., Amitani, I., Baskin, R.J. and Kowalczykowski, S.C. (2006) Direct observation of individual RecA filaments assembling on single DNA molecules. Nature, 443, 875-878. (Pubitemid 44622700)
19. Kim, Y.T., Tabor, S., Churchich, J.E. and Richardson, C.C. (1992) Interactions of gene 2.5 protein and DNA polymerase of bacteriophage T7. J. Biol. Chem., 267, 15032-15040.
20. Honda, M., Park, J., Pugh, R.A., Ha, T. and Spies, M. (2009) Singlemolecule analysis reveals differential effect of ssDNA-binding proteins on DNA translocation by XPD helicase. Mol. Cell, 35, 694-703.
21. Arambula, J.F., Ramisetty, S.R., Baranger, A.M. and Zimmerman, S.C. (2009) A simple ligand that selectively targets CUG trinucleotide repeats and inhibits MBNL protein binding. Proc. Natl Acad. Sci. USA, 106, 16068-16073.
22. Mammen, M., Choi, S.K. and Whitesides, G.M. (1998) Polyvalent interactions in biological systems: Implications for design and use of multivalent ligands and inhibitors. Angew. Chem. Int. Ed., 37, 2755-2794.
23. Childs-Disney, J.L., Hoskins, J., Rzuczek, S.G., Thornton, C.A. and Disney, M.D. (2012) Rationally designed small molecules targeting the RNA that causes myotonic dystrophy type 1 are potently bioactive. ACS Chem. Biol., 7, 856-862.
24. Wong, C.H., Richardson, S.L., Ho, Y.J., Lucas, A.M., Tuccinardi, T., Baranger, A.M. and Zimmerman, S.C. (2012) Investigating the binding mode of an inhibitor of the MBNL1. RNA complex in myotonic dystrophy Type 1 (DM1) leads to the unexpected discovery of a DNA-selective binder. ChemBioChem, 13, 2505-2509.
25. Zimmerman, S.C., Lamberson, C.R., Cory, M. and Fairley, T.A. (1989) Topologically Constrained bifunctional intercalators-DNA intercalation by a macrocyclic bisacridine. J. Am. Chem. Soc., 111, 6805-6809. (Pubitemid 19208941)
26. Fechter, E.J., Olenyuk, B. and Dervan, P.B. (2004) Design of a sequence-specific DNA bisintercalator. Angew. Chem. Int. Ed. Engl., 43, 3591-3594. (Pubitemid 39257546)
27. Holman, G.G., Zewail-Foote, M., Smith, A.R., Johnson, K.A. and Iverson, B.L. (2011) A sequence-specific threading tetra-intercalator with an extremely slow dissociation rate constant. Nat. Chem., 3, 875-881.
28. Van den Wildenberg, S.M., Prevo, B. and Peterman, E.J. (2011) Single molecule analysis. Methods, 783, 81-99.
29. Reck-Peterson, S.L., Derr, N.D. and Stuurman, N. (2010) Imaging single molecules using total internal reflection fluorescence microscopy (TIRFM). Cold Spring Harb. Protoc., 2010, pdb.top1173.
30. Warf, M.B. and Berglund, J.A. (2007) MBNL binds similar RNA structures in the CUG repeats of myotonic dystrophy and its pre-mRNA substrate cardiac troponin T. RNA, 13, 2238-2251. (Pubitemid 350127564)
31. Cass, D., Hotchko, R., Barber, P., Jones, K., Gates, D.P. and Berglund, J.A. (2011) The four Zn fingers of MBNL1 provide a flexible platform for recognition of its RNA binding elements. BMC Mol. Biol., 12, 20.
32. Qin, F., Auerbach, A. and Sachs, F. (1996) Estimating singlechannel kinetic parameters from idealized patch-clamp data containing missed events. Biophys. J., 70, 264-280. (Pubitemid 26021465)
33. Teplova, M. and Patel, D.J. (2008) Structural insights into RNA recognition by the alternative-splicing regulator muscleblind-like MBNL1. Nat. Struct. Mol. Biol., 15, 1343-1351.
34. Feng, B.Y. and Shoichet, B.K. (2006) A detergent-based assay for the detection of promiscuous inhibitors. Nat. Protoc., 1, 550-553.
35. Vamosi, G., Gohlke, C. and Clegg, R.M. (1996) Fluorescence characteristics of 5-carboxytetramethylrhodamine linked covalently to the 5' end of oligonucleotides: multiple conformers of single-stranded and double-stranded dye-DNA complexes. Biophys. J., 71, 972-994. (Pubitemid 26289181)
36. Qu, P., Chen, X.D., Zhou, X.X., Li, X. and Zhao, X.S. (2009) Fluorescence quenching of TMR by guanosine in oligonucleotides. Sci. China, Ser. B, 52, 1653-1659.
37. Xu, Y. and Komiyama, M. (2012) Structure, function and targeting of human telomere RNA. Methods, 57, 100-105.
38. Vicens, Q. and Westhof, E. (2003) RNA as a drug target: the case of aminoglycosides. ChemBioChem, 4, 1018-1023. (Pubitemid 37267590)
39. Vicens, Q. (2009) RNA's coming of age as a drug target. J. Incl. Phenom. Macro., 65, 171-188.
40. Cooper, T.A., Wan, L. and Dreyfuss, G. (2009) RNA and disease. Cell, 136, 777-793.
41. Fu, Y., Ramisetty, S.R., Hussain, N. and Baranger, A.M. (2012) MBNL1-RNA recognition: contributions of MBNL1 sequence and RNA conformation. ChemBioChem, 13, 112-119.
42. Laurent, F.X., Sureau, A., Klein, A.F., Trouslard, F., Gasnier, E., Furling, D. and Marie, J. (2012) New function for the RNA helicase p68/DDX5 as a modifier of MBNL1 activity on expanded CUG repeats. Nucleic Acids Res., 40, 3159-3171.
43. Stelzer, A.C., Frank, A.T., Kratz, J.D., Swanson, M.D., Gonzalez-Hernandez, M.J., Lee, J., Andricioaei, I., Markovitz, D.M. and Al-Hashimi, H.M. (2011) Discovery of selective bioactive small molecules by targeting an RNA dynamic ensemble. Nat. Chem. Biol., 7, 553-559.