TMPyP4 porphyrin distorts RNA G-quadruplex structures of the disease-associated r(GGGGCC)n repeat of the C9orf72 gene and blocks interaction of RNAbinding proteins

Journal of Biological Chemistry

Volumn 289, Issue 8, 2014, Pages 4653-4659

  Zamiri, Bita ^a   Reddy, Kaalak ^a   Macgregor, Robert B ^a   Pearson, Christopher E ^a,b  

^a UNIVERSITY OF TORONTO   (Canada)

^b HOSPITAL FOR SICK CHILDREN   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEINS; RNA;

AMYOTROPHIC LATERAL SCLEROSIS; FRONTOTEMPORAL DEMENTIAS; G-QUADRUPLEX STRUCTURE; G-QUADRUPLEXES; PROTEIN INTERACTION; RNA-BINDING PROTEIN; SECONDARY STRUCTURES;

DNA SEQUENCES;

5,10,15,20 TETRA(N METHYL 4 PYRIDYL)PORPHYRIN; ASF PROTEIN; NUCLEIC ACID BINDING PROTEIN; PORPHYRIN; RNA BINDING PROTEIN; SF2 PROTEIN; UNCLASSIFIED DRUG;

ARTICLE; C9ORF72 GENE; DISEASE ASSOCIATION; G QUADRUPLEX STRUCTURE; GENE; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN INTERACTION; RNA BINDING; RNA SEQUENCE; RNA STRUCTURE; RNA TRANSLATION;

AMYOTROPHIC LATERAL SCLEROSIS (LOU GEHRIG DISEASE); ASF/SF2; C9ORF72; G-QUADRUPLEX; HNRNPA1; RNA; RNA STRUCTURE; RNA-BINDING PROTEIN; RNA-PROTEIN INTERACTION; TMPYP4;

AMYOTROPHIC LATERAL SCLEROSIS; BASE SEQUENCE; DNA REPEAT EXPANSION; FRONTOTEMPORAL DEMENTIA; G-QUADRUPLEXES; HETEROGENEOUS-NUCLEAR RIBONUCLEOPROTEIN GROUP A-B; HUMANS; NUCLEAR PROTEINS; PORPHYRINS; PROTEIN BINDING; PROTEINS; RNA-BINDING PROTEINS;

EID: 84894465709     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.C113.502336     Document Type: Article

References (51)

1. Turner, M. R., Hardiman, O., Benatar, M., Brooks, B. R., Chio, A., de Carvalho, M., Ince, P. G., Lin, C., Miller, R. G., Mitsumoto, H., Nicholson, G., Ravits, J., Shaw, P. J., Swash, M., Talbot, K., Traynor, B. J., Van den Berg, L. H., Veldink, J. H., Vucic, S., and Kiernan, M. C. (2013) Controversies and priorities in amyotrophic lateral sclerosis. Lancet Neurol. 12, 310-322
2. DeJesus-Hernandez, M., Mackenzie, I. R., Boeve, B. F., Boxer, A. L., Baker, M., Rutherford, N. J., Nicholson, A. M., Finch, N. A., Flynn, H., Adamson, J., Kouri, N., Wojtas, A., Sengdy, P., Hsiung, G. Y., Karydas, A., Seeley, W. W., Josephs, K. A., Coppola, G., Geschwind, D. H., Wszolek, Z. K., Feldman, H., Knopman, D. S., Petersen, R. C., Miller, B. L., Dickson, D. W., Boylan, K. B., Graff-Radford, N. R., and Rademakers, R. (2011) Expanded GGGGCC hexanucleotide repeat in noncoding region of C9orf72 causes chromosome 9p-linked FTD and ALS. Neuron 72, 245-256
3. Renton, A. E., Majounie, E., Waite, A., Simón-Sánchez, J., Rollinson, S., Gibbs, J. R., Schymick, J. C., Laaksovirta, H., van Swieten, J. C., Myllykangas, L., Kalimo, H., Paetau, A., Abramzon, Y., Remes, A. M., Kaganovich, A., Scholz, S. W., Duckworth, J., Ding, J., Harmer, D. W., Hernandez, D. G., Johnson, J. O., Mok, K., Ryten, M., Trabzuni, D., Guerreiro, R. J., Orrell, R. W., Neal, J., Murray, A., Pearson, J., Jansen, I. E., Sondervan, D., Seelaar, H., Blake, D., Young, K., Halliwell, N., Callister, J. B., Toulson, G., Richardson, A., Gerhard, A., Snowden, J., Mann, D., Neary, D., Nalls, M. A., Peuralinna, T., Jansson, L., Isoviita, V. M., Kaivorinne, A. L., Hölttä-Vuori, M., Ikonen, E., Sulkava, R., Benatar, M., Wuu, J., Chiò, A., Restagno, G., Borghero, G., Sabatelli, M., Heckerman, D., Rogaeva, E., Zinman, L., Rothstein, J. D., Sendtner, M., Drepper, C., Eichler, E. E., Alkan, C., Abdullaev, Z., Pack, S. D., Dutra, A., Pak, E., Hardy, J., Singleton, A., Williams, N. M., Heutink, P., Pickering-Brown, S., Morris, H. R., Tienari, P. J., and Traynor, B. J. (2011) A hexanucleotide repeat expansion in C9orf72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72, 257-268
4. Gómez-Tortosa, E., Gallego, J., Guerrero-López, R., Marcos, A., Gil-Neciga, E., Sainz, M. J., Díaz, A., Franco-Macías, E., Trujillo-Tiebas, M. J., Ayuso, C., and Pérez-Pérez, J. (2013) C9orf72 hexanucleotide expansions of 20-22 repeats are associated with frontotemporal deterioration. Neurology 80, 366-370
5. Shin, J., Charizanis, K., and Swanson, M. S. (2009) Pathogenic RNAs in microsatellite expansion disease. Neurosci. Lett. 466, 99-102
6. Mori, K., Lammich, S., Mackenzie, I. R., Forné, I., Zilow, S., Kretzschmar, H., Edbauer, D., Janssens, J., Kleinberger, G., Cruts, M., Herms, J., Neumann, M., Van Broeckhoven, C., Arzberger, T., and Haass, C. (2013) hnRNP A3 binds to GGGGCC repeats and is a constituent of p62-positive/ TDP43-negative inclusions in the hippocampus of patients with C9orf72 mutations. Acta Neuropathol. 125, 413-423
7. Reddy, K., Zamiri, B., Stanley, S. Y., Macgregor, R. B., Jr., and Pearson, C. E. (2013) The disease-associated r(GGGGCC)n repeat from the C9orf72 gene forms tract length-dependent uni-and multimolecular RNA G-quadruplex structures. J. Biol. Chem. 288, 9860-9866
8. Xu, Z., Poidevin, M., Li, X., Li, Y., Shu, L., Nelson, D. L., Li, H., Hales, C. M., Gearing, M., Wingo, T. S., and Jin, P. (2013) Expanded GGGGCC repeat RNA associated with amyotrophic lateral sclerosis and frontotemporal dementia causes neurodegeneration. Proc. Natl. Acad. Sci. U.S.A. 110, 7778-7783
9. Lee, Y. B., Chen, H. J., Peres, J. N., Gomez-Deza, J., Attig, J., Stalekar, M., Troakes, C., Nishimura, A. L., Scotter, E. L., Vance, C., Adachi, Y., Sardone, V., Miller, J. W., Smith, B. N., Gallo, J. M., Ule, J., Hirth, F., Rogelj, B., Houart, C., and Shaw, C. E. (2013) Hexanucleotide repeats in ALS/FTD form length-dependent RNA foci, sequester RNA binding proteins, and are neurotoxic. Cell Rep. 5, 1178-1186
10. Kim, H. J., Kim, N. C., Wang, Y. D., Scarborough, E. A., Moore, J., Diaz, Z., MacLea, K. S., Freibaum, B., Li, S., Molliex, A., Kanagaraj, A. P., Carter, R., Boylan, K. B., Wojtas, A. M., Rademakers, R., Pinkus, J. L., Greenberg, S. A., Trojanowski, J. Q., Traynor, B. J., Smith, B. N., Topp, S., Gkazi, A. S., Miller, J., Shaw, C. E., Kottlors, M., Kirschner, J., Pestronk, A., Li, Y. R., Ford, A. F., Gitler, A. D., Benatar, M., King, O. D., Kimonis, V. E., Ross, E. D., Weihl, C. C., Shorter, J., and Taylor, J. P. (2013) Mutations in prionlike domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature 495, 467-473
11. Reddy, K., and Pearson, C. E. (2013) RAN rranslation: Fragile X in the running. Neuron 78, 405-408
12. Ash, P. E., Bieniek, K. F., Gendron, T. F., Caulfield, T., Lin, W. L., Dejesus-Hernandez, M., van Blitterswijk, M. M., Jansen-West, K., Paul, J. W., 3rd, Rademakers, R., Boylan, K. B., Dickson, D. W., and Petrucelli, L. (2013) Unconventional translation of C9orf72 GGGGCC expansion generates insoluble polypeptides specific to c9FTD/ALS. Neuron 77, 639-646
13. Zu, T., Liu, Y., Bañez-Coronel, M., Reid, T., Pletnikova, O., Lewis, J., Miller, T. M., Harms, M. B., Falchook, A. E., Subramony, S. H., Ostrow, L. W., Rothstein, J. D., Troncoso, J. C., and Ranum, L. P. (2013) RAN proteins and RNA foci from antisense transcripts in C9orf72 ALS and frontotemporal dementia. Proc. Natl. Acad. Sci. U.S.A. 110, E4968-E4977
14. Mori, K., Arzberger, T., Grässer, F. A., Gijselinck, I., May, S., Rentzsch, K., Weng, S. M., Schludi, M. H., van der Zee, J., Cruts, M., Van Broeckhoven, C., Kremmer, E., Kretzschmar, H. A., Haass, C., and Edbauer, D. (2013) Bidirectional transcripts of the expanded C9orf72 hexanucleotide repeat are translated into aggregating dipeptide repeat proteins. Acta Neuropathol. 126, 881-893
15. Gendron, T. F., Bieniek, K. F., Zhang, Y. J., Jansen-West, K., Ash, P. E., Caulfield, T., Daughrity, L., Dunmore, J. H., Castanedes-Casey, M., Chew, J., Cosio, D. M., van Blitterswijk, M., Lee, W. C., Rademakers, R., Boylan, K. B., Dickson, D. W., and Petrucelli, L. (2013) Antisense transcripts of the expanded C9orf72 hexanucleotide repeat form nuclear RNA foci and undergo repeat-associated non-ATG translation in c9FTD/ALS. Acta Neuropathol. 126, 829-844
16. Zu, T., Gibbens, B., Doty, N. S., Gomes-Pereira, M., Huguet, A., Stone, M. D., Margolis, J., Peterson, M., Markowski, T. W., Ingram, M. A., Nan, Z., Forster, C., Low, W. C., Schoser, B., Somia, N. V., Clark, H. B., Schmechel, S., Bitterman, P. B., Gourdon, G., Swanson, M. S., Moseley, M., and Ranum, L. P. (2011) Non-ATG-initiated translation directed by microsatellite expansions. Proc. Natl. Acad. Sci. U.S.A. 108, 260-265
17. Pearson, C. E. (2011) Repeat associated non-ATG translation initiation: one DNA, two transcripts, seven reading frames, potentially nine toxic entities! PLoS Genet. 7, e1002018
18. Wheeler, T. M., Sobczak, K., Lueck, J. D., Osborne, R. J., Lin, X., Dirksen, R. T., and Thornton, C. A. (2009) Reversal ofRNAdominance by displacement of protein sequestered on triplet repeat RNA. Science 325, 336-339
19. Fratta, P., Mizielinska, S., Nicoll, A. J., Zloh, M., Fisher, E. M., Parkinson, G., and Isaacs, A. M. (2012) C9orf72 hexanucleotide repeat associated with amyotrophic lateral sclerosis and frontotemporal dementia forms RNA G-quadruplexes. Sci. Rep. 2, 1016
20. Gellert, M., Lipsett, M. N., and Davies, D. R. (1962) Helix formation by guanylic acid. Proc. Natl. Acad. Sci. U.S.A. 48, 2013-2018
21. Sen, D., and Gilbert, W. (1990) A sodium-potassium switch in the formation of four-stranded G4-DNA. Nature 344, 410-414
22. Miura, T., Benevides, J. M., and Thomas, G. J., Jr. (1995) A phase diagram for sodium and potassium ion control of polymorphism in telomeric DNA. J. Mol. Biol. 248, 233-238
23. Biffi, G., Tannahill, D., McCafferty, J., and Balasubramanian, S. (2013) Quantitative visualization of DNA G-quadruplex structures in human cells. Nat. Chem. 5, 182-186
24. Xu, Y., and Komiyama, M. (2013) Evidence for G-quadruplex DNA in human cells. Chembiochem 14, 927-928
25. Eddy, J., and Maizels, N. (2008) Conserved elements with potential to form polymorphic G-quadruplex structures in the first intron of human genes. Nucleic Acids Res. 36, 1321-1333
26. Melko, M., and Bardoni, B. (2010) The role of G-quadruplex in RNA metabolism: involvement of FMRP and FMR2P. Biochimie 92, 919-926
27. Darnell, J. C., Jensen, K. B., Jin, P., Brown, V., Warren, S. T., and Darnell, R. B. (2001) FragileXmental retardation protein targetsGquartetmRNAs important for neuronal function. Cell 107, 489-499
28. Brown, V., Jin, P., Ceman, S., Darnell, J. C., O'Donnell, W. T., Tenenbaum, S. A., Jin, X., Feng, Y., Wilkinson, K. D., Keene, J. D., Darnell, R. B., and Warren, S. T. (2001) Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome. Cell 107, 477-487
29. Bugaut, A., and Balasubramanian, S. (2012) 5UTR RNA G-quadruplexes: translation regulation and targeting. Nucleic Acids Res. 40, 4727-4741
30. Subramanian, M., Rage, F., Tabet, R., Flatter, E., Mandel, J. L., and Moine, H. (2011) G-quadruplex RNA structure as a signal for neurite mRNA targeting. EMBO Rep. 12, 697-704
31. Darnell, J. C., Warren, S. T., and Darnell, R. B. (2004) The fragile X mental retardation protein, FMRP, recognizes G-quartets. Ment. Retard. Dev. Disabil. Res. Rev. 10, 49-52
32. Düchler, M. (2012) G-quadruplexes: targets and tools in anticancer drug design. J. Drug Target 20, 389-400
33. Morris, M. J., Wingate, K. L., Silwal, J., Leeper, T. C., and Basu, S. (2012) The porphyrin TMPyP4 unfolds the extremely stable G-quadruplex in MT3-MMP mRNA and alleviates its repressive effect to enhance translation in eukaryotic cells. Nucleic Acids Res. 40, 4137-4145
34. Weisman-Shomer, P., Cohen, E., Hershco, I., Khateb, S., Wolfovitz-Barchad, O., Hurley, L. H., and Fry, M. (2003) The cationic porphyrin TMPyP4 destabilizes the tetraplex form of the fragile X syndrome expanded sequence d(CGG)n. Nucleic Acids Res. 31, 3963-3970
35. Ofer, N., Weisman-Shomer, P., Shklover, J., and Fry, M. (2009) The quadruplex r(CGG)n destabilizing cationic porphyrin TMPyP4 cooperates with hnRNPs to increase the translation efficiency of fragile X premutation mRNA. Nucleic Acids Res. 37, 2712-2722
36. Oostra, B. A., and Willemsen, R. (2009) FMR1: a gene with three faces. Biochim Biophys Acta 1790, 467-477
37. Cantor, C. R., Warshaw, M. M., and Shapiro, H. (1970) Oligonucleotide interactions. Circular dichroism studies of the conformation of deoxyoligonucleotides. Biopolymers 9, 1059-1077
38. Keating, L. R., and Szalai, V. A. (2004) Parallel-stranded guanine quadruplex interactions with a copper cationic porphyrin. Biochemistry 43, 15891-15900
39. Wei, C., Wang, L., Jia, G., Zhou, J., Han, G., and Li, C. (2009) The binding mode of porphyrins with cation side arms to (TG4T)4 G-quadruplex: spectroscopic evidence. Biophys. Chem. 143, 79-84
40. Balagurumoorthy, P., and Brahmachari, S. K. (1994) Structure and stability of human telomeric sequence. J. Biol. Chem. 269, 21858-21869
41. Phan, A. T., Kuryavyi, V., and Patel, D. J. (2006)DNAarchitecture: fromG to Z. Curr. Opin. Struct. Biol. 16, 288-298
42. Martino, L., Pagano, B., Fotticchia, I., Neidle, S., and Giancola, C. (2009) Shedding light on the interaction between TMPyP4 and human telomeric quadruplexes. J Phys Chem B 113, 14779-14786
43. Lane, A. N., Chaires, J. B., Gray, R. D., and Trent, J. O. (2008) Stability and kinetics of G-quadruplex structures. Nucleic Acids Res. 36, 5482-5515
44. Zhang, Q. S., Manche, L., Xu, R. M., and Krainer, A. R. (2006) hnRNP A1 associates with telomere ends and stimulates telomerase activity. RNA 12, 1116-1128
45. Flynn, R. L., Centore, R. C., O'Sullivan, R. J., Rai, R., Tse, A., Songyang, Z., Chang, S., Karlseder, J., and Zou, L. (2011) TERRA and hnRNPA1 orchestrate an RPA-to-POT1 switch on telomeric single-stranded DNA. Nature 471, 532-536
46. Nakagama, H., Higuchi, K., Tanaka, E., Tsuchiya, N., Nakashima, K., Katahira, M., and Fukuda, H. (2006) Molecular mechanisms for maintenance of G-rich short tandem repeats capable of adopting G4 DNA structures. Mutat. Res. 598, 120-131
47. 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
48. 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
49. Lagier-Tourenne, C., Baughn, M., Rigo, F., Sun, S., Liu, P., Li, H. R., Jiang, J., Watt, A. T., Chun, S., Katz, M., Qiu, J., Sun, Y., Ling, S. C., Zhu, Q., Polymenidou, M., Drenner, K., Artates, J. W., McAlonis-Downes, M., Markmiller, S., Hutt, K. R., Pizzo, D. P., Cady, J., Harms, M. B., Baloh, R. H., Vandenberg, S. R., Yeo, G. W., Fu, X. D., Bennett, C. F., Cleveland, D. W., and Ravits, J. (2013) Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration. Proc. Natl. Acad. Sci. U.S.A. 110, E4530-E4539
50. Sareen, D., O'Rourke, J. G., Meera, P., Muhammad, A. K., Grant, S., Simpkinson, M., Bell, S., Carmona, S., Ornelas, L., Sahabian, A., Gendron, T., Petrucelli, L., Baughn, M., Ravits, J., Harms, M. B., Rigo, F., Bennett, C. F., Otis, T. S., Svendsen, C. N., and Baloh, R. H. (2013) Targeting RNA foci in iPSC-derived motor neurons from ALS patients with a C9orf72 repeat expansion. Sci. Transl. Med. 5, 208ra149
51. Donnelly, C. J., Zhang, P. W., Pham, J. T., Heusler, A. R., Mistry, N. A., Vidensky, S., Daley, E. L., Poth, E. M., Hoover, B., Fines, D. M., Maragakis, N., Tienari, P. J., Petrucelli, L., Traynor, B. J., Wang, J., Rigo, F., Bennett, C. F., Blackshaw, S., Sattler, R., and Rothstein, J. D. (2013) RNA toxicity from the ALS/FTD C9orf72 expansion is mitigated by antisense intervention. Neuron 80, 415-428