C9orf72 nucleotide repeat structures initiate molecular cascades of disease

Nature

Volumn 507, Issue 7491, 2014, Pages 195-200

  Haeusler, Aaron R ^a,b   Donnelly, Christopher J ^a,b   Periz, Goran ^a,b   Simko, Eric A J ^a,b   Shaw, Patrick G ^a   Kim, Min Sik ^a   Maragakis, Nicholas J ^b   Troncoso, Juan C ^b   Pandey, Akhilesh ^a   Sattler, Rita ^a,b   Rothstein, Jeffrey D ^a,b   Wang, Jiou ^a,b  

^a JOHNS HOPKINS UNIVERSITY   (United States)

^b JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; DNA HYBRID; GUANINE QUADRUPLEX; NUCLEOLIN; RNA;

DNA; MOLECULAR ANALYSIS; NEUROLOGY; PATHOLOGY; POLYMORPHISM; PROTEIN;

AMYOTROPHIC LATERAL SCLEROSIS; ARTICLE; CONFORMATION; CONTROLLED STUDY; DEGENERATIVE DISEASE; DNA POLYMORPHISM; FRONTOTEMPORAL DEMENTIA; GENE STRUCTURE; GENETIC TRANSCRIPTION; HUMAN; HUMAN TISSUE; MOLECULAR MECHANICS; NUCLEIC ACID STRUCTURE; NUCLEOTIDE REPEAT; PRIORITY JOURNAL; PROTEIN BINDING; STRESS;

AMYOTROPHIC LATERAL SCLEROSIS; B-LYMPHOCYTES; BASE SEQUENCE; CELL NUCLEOLUS; DNA; DNA REPEAT EXPANSION; FRONTOTEMPORAL DEMENTIA; G-QUADRUPLEXES; HEK293 CELLS; HUMANS; MODELS, MOLECULAR; NEURONS; OPEN READING FRAMES; PHOSPHOPROTEINS; RIBONUCLEOPROTEINS; RNA; RNA-BINDING PROTEINS; STRESS, PHYSIOLOGICAL; TRANSCRIPTION, GENETIC;

EID: 84896259966     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature13124     Document Type: Article

References (46)

1. Richard, G. F., Kerrest, A. & Dujon, B. Comparative genomics and molecular dynamics of DNA repeats in eukaryotes. Microbiol. Mol. Biol. Rev. 72, 686-727 (2008).
2. DeJesus-Hernandez, M. et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72, 245-256 (2011).
3. Renton, A. E. et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72, 257-268 (2011).
4. Kiernan, M. C. et al. Amyotrophic lateral sclerosis. Lancet 377, 942-955 (2011).
5. Majounie, E. et al. Frequency of the C9orf72 hexanucleotide repeat expansion in patients withamyotrophic lateral sclerosis and frontotemporal dementia: a crosssectional study. Lancet Neurol. 11, 323-330 (2012).
6. Rademakers, R., Neumann, M. & Mackenzie, I. R. Advances in understanding the molecular basis of frontotemporal dementia. Nature Rev. Neurol. 8, 423-434 (2012).
7. van Langenhove, T., van der Zee, J. & van Broeckhoven, C. The molecular basis of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum. Ann. Med. 44, 817-828 (2012).
8. Rollinson, S. et al. Analysis of the hexanucleotide repeat inC9ORF72 in Alzheimer's disease. Neurobiol. Aging 33, 1846.e5-1846.e6 (2012).
9. Kohli, M. A. et al. Repeat expansions in the C9ORF72 gene contribute to Alzheimer's disease in Caucasians. Neurobiol. Aging 34, 1519.e5-1519.e12 (2013).
10. Majounie, E. et al. Repeat expansion in C9ORF72 in Alzheimer's disease. N. Engl. J. Med. 366, 283-284 (2012).
11. Hensman-Moss, D. J. et al. C9orf72 expansions are the most common genetic cause of Huntington disease phenocopies. Neurology 82, 292-299 (2014).
12. Rutherford, N. J. et al. Length of normal alleles of C9ORF72 GGGGCC repeat do not influence disease phenotype. Neurobiol. Aging 33, 2950.e5-2950.e7 (2012).
13. Mirkin, S. M. Expandable DNA repeats and human disease. Nature 447, 932-940 (2007).
14. La Spada, A. R. & Taylor, J. P. Repeat expansion disease: progress and puzzles in disease pathogenesis. Nature Rev. Genet. 11, 247-258 (2010).
15. Fratta, P. et al. C9orf72 hexanucleotide repeat associated with amyotrophic lateral sclerosis and frontotemporal dementia forms RNA G-quadruplexes. Sci. Rep. 2, 1016 (2012).
16. Reddy, K., Zamiri, B., Stanley, S. Y. R., Macgregor, R. B.& Pearson, C. E. The Diseaseassociated r(GGGGCC)n repeat from the C9orf72 gene forms tract lengthdependent uni- and multimolecular RNA G-quadruplex structures. J. Biol. Chem. 288, 9860-9866 (2013).
17. Xu, Z. et al. Expanded GGGGCC repeat RNA associated with amyotrophic lateral sclerosis and frontotemporal dementia causes neurodegeneration. Proc. Natl Acad. Sci. USA 110, 7778-7783 (2013).
18. Mori, K. et al. The C9orf72 GGGGCC repeat is translated into aggregating dipeptide-repeat proteins in FTLD/ALS. Science 339, 1335-1338 (2013).
19. Ash, P. E. A. et al. Unconventional translation of C9ORF72 GGGGCC expansion generates insoluble polypeptides specific to c9FTD/ALS. Neuron 77, 639-646 (2013).
20. Donnelly, C. J. et al. RNA toxicity from the ALS/FTD C9ORF72 expansion is mitigated by antisense intervention. Neuron 80, 415-428 (2013).
21. Lagier-Tourenne, C. et al. Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration. Proc. Natl Acad. Sci. USA 110, E4530-E4539 (2013).
22. Sareen, D. et al. Targeting RNA foci in iPSC-derived motor neurons from ALS patients with a C9ORF72 repeat expansion. Sci. Transl. Med. 5, 208ra149 (2013).
23. Zu, T. et al. RAN proteins and RNA foci fromantisense transcripts in C9ORF72 ALS and frontotemporal dementia. Proc. Natl Acad. Sci. USA, (2013).
24. Gellert, M., Lipsett, M. N. & Davies, D. R. Helix formation by guanylic acid. Proc. Natl Acad. Sci. USA 48, 2013 (1962).
25. Huppert, J. L. Four-stranded nucleic acids: structure, function and targeting of G-quadruplexes. Chem. Soc. Rev. 37, 1375 (2008).
26. Maxam, A. M. & Gilbert, W. A new method for sequencing DNA. Proc. Natl Acad. Sci. USA 74, 560-564 (1977).
27. Kumari, S., Bugaut, A., Huppert, J. L. & Balasubramanian, S. An RNA G-quadruplex in the 59 UTR of the NRAS proto-oncogene modulates translation. Nature Chem. Biol. 3, 218-221 (2007).
28. Biffi, G., Tannahill, D., McCafferty, J. & Balasubramanian, S. Quantitative visualization of DNA G-quadruplex structures in human cells. Nature Chem. 5, 182-186 (2013).
29. Li, H. et al. Ultrasensitive label-free amplified colorimetric detection of p53 based on G-quadruplex MBzymes. Biosens. Bioelectron. 50, 180-185 (2013).
30. Ong, S.-E. et al. Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol. Cell. Proteomics 1, 376-386 (2002).
31. Abdelmohsen, K. & Gorospe, M. RNA-binding protein nucleolin in disease. RNA Biol. 9, 799-808 (2012).
32. Eulalio, A., Behm-Ansmant, I. & Izaurralde, E. P bodies: at the crossroads of posttranscriptional pathways. Nature Rev. Mol. Cell Biol. 8, 9-22 (2007).
33. Boulon, S., Westman, B. J., Hutten, S., Boisvert, F.-M. & Lamond, A. I. The nucleolus under stress. Mol. Cell 40, 216-227 (2010).
34. Hetman, M. & Pietrzak, M. Emerging roles of the neuronal nucleolus. Trends Neurosci. 35, 305-314 (2012).
35. Hazel, P., Huppert, J., Balasubramanian, S. & Neidle, S. Loop-length-dependent folding of G-quadruplexes. J. Am. Chem. Soc. 126, 16405-16415 (2004).
36. Hellman, L. M. & Fried, M. G. Electrophoretic mobility shift assay (EMSA) for detecting protein-nucleic acid interactions. Nature Protocols 2, 1849-1861 (2007).
37. Sun, D. & Hurley, L. H. in Methods in Molecular Biology (ed. Baumann, P.) 608, 65-79 (Humana, 2009).
38. Hsu, R.-J. et al. Long tract of untranslated CAG repeats is deleterious in transgenic mice. PLoS ONE 6, e16417 (2011).
39. Reddy, K. et al. Determinants of R-loop formation at convergent bidirectionally transcribed trinucleotide repeats. Nucleic Acids Res. 39, 1749-1762 (2011).
40. Iioka, H., Loiselle, D., Haystead, T. A. & Macara, I. G. Efficient detection of RNAprotein interactions using tethered RNAs. Nucleic Acids Res. 39, e53 (2011).
41. Wiśniewski, J. R., Zougman, A., Nagaraj, N. & Mann, M. Universal sample preparation method for proteome analysis. Nature Methods 6, 359-362 (2009).
42. Rappsilber, J., Ishihama, Y. & Mann, M. Stop and go extraction tips for matrixassisted laser desorption/ionization, nanoelectrospray, and LC/MS sample pretreatment in proteomics. Anal. Chem. 75, 663-670 (2003).
43. Matunis, M. J., Xing, J. & Dreyfuss, G. The hnRNP F protein: unique primary structure, nucleic acid-binding properties, and subcellular localization. Nucleic Acids Res. 22, 1059-1067 (1994).
44. Tsoi, H., Lau, T. C.-K., Tsang, S.-Y., Lau, K.-F. & Chan, H. Y. E. CAG expansion induces nucleolar stress inpolyglutamine diseases. Proc.NatlAcad. Sci.USA109, 13428-13433 (2012).
45. Almeida, S. et al.Modeling key pathological features of frontotemporal dementia with C9ORF72 repeat expansion in iPSC-derived human neurons. Acta Neuropathol. 126, 385-399 (2013).
46. Uemura, M. et al. Overexpression of ribosomal RNA inprostate cancer iscommonbut not linked to rDNA promoter hypomethylation. Oncogene 31, 1254-1263 (2012).