Invited Review: Decoding the pathophysiological mechanisms that underlie RNA dysregulation in neurodegenerative disorders: A review of the current state of the art

Neuropathology and Applied Neurobiology

Volumn 41, Issue 2, 2015, Pages 109-134

  Walsh, Matthew J ^a   Cooper Knock, Johnathan ^a   Dodd, Jennifer E ^a   Stopford, Matthew J ^a   Mihaylov, Simeon R ^a   Kirby, Janine ^a   Shaw, Pamela J ^a   Hautbergue, Guillaume M ^a  

^a UNIVERSITY OF SHEFFIELD   (United Kingdom)

Author keywords

Altered gene expression; Neurodegeneration; Protein loss of function; RNA mediated diseases; RNA protein toxic gain of function

Indexed keywords

COPPER ZINC SUPEROXIDE DISMUTASE; FUSED IN SARCOMA PROTEIN; MESSENGER RNA; RNA; SURVIVAL MOTOR NEURON PROTEIN; TAR DNA BINDING PROTEIN;

AMYOTROPHIC LATERAL SCLEROSIS; C9ORF72 AMYOTROPHIC LATERAL SCLEROSIS; CHROMATIN; CHROMATIN REMODELLING; CHROMOSOME ABERRATION; DEGENERATIVE DISEASE; GAIN OF FUNCTION MUTATION; GENE EXPRESSION; HUMAN; HUNTINGTON CHOREA; LOSS OF FUNCTION MUTATION; MEDICAL RESEARCH; NERVE CELL; NERVE DEGENERATION; NEUROPATHOLOGY; NONHUMAN; POINT MUTATION; PRIORITY JOURNAL; REVIEW; RNA METABOLISM; SPINAL MUSCULAR ATROPHY; SPINOCEREBELLAR DEGENERATION; ANIMAL; GENETICS;

ANIMALS; HUMANS; NEURODEGENERATIVE DISEASES; RNA;

EID: 84921721593     PISSN: 03051846     EISSN: 13652990     Source Type: Journal    
DOI: 10.1111/nan.12187     Document Type: Review

References (249)

1. Walker FO. Huntington's disease. Lancet 2007; 369: 218-228
2. MacDonald ME, Ambrose CM, Duyao MP, Myers RH, Lin C, Srinidhi L, Barnes G, Taylor SA, James M, Groot N, MacFarlane H, Jenkins B, Anderson MA, Wexler NS, Gusella JF, Bates GP, Baxendale S, Hummerich H, Kirby S, North M, Youngman S, Mott R, Zehetner G, Sedlacek Z, Poustka A, Frischauf AM, Lehrach H, Buckler AJ, Church D, Doucettestamm L, Odonovan MC, Ribaramirez L, Shah M, Stanton VP, Strobel SA, Draths KM, Wales JL, Dervan P, Housman DE, Altherr M, Shiang R, Thompson L, Fielder T, Wasmuth JJ, Tagle D, Valdes J, Elmer L, Allard M, Castilla L, Swaroop M, Blanchard K, Collins FS, Snell R, Holloway T, Gillespie K, Datson N, Shaw D, Harper PS. A novel gene containing a trinucleotide repeat that is expanded and unstable on huntingtons-disease chromosomes. Cell 1993; 72: 971-983
3. LaSpada AR, Paulson HL, Fischbeck KH. Trinucleotide repeat expansion in neurological disease. Ann Neurol 1994; 36: 814-822
4. Whaley NR, Fujioka S, Wszolek ZK. Autosomal dominant cerebellar ataxia type I: a review of the phenotypic and genotypic characteristics. Orphanet J Rare Dis 2011; 6: 33
5. Lunn MR, Wang CH. Spinal muscular atrophy. Lancet 2008; 371: 2120-2133
6. Lefebvre S, Bürglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C, Millasseau P, Zeviani M, Le Paslier D, Frézal J, Cohen D, Weissenbach J, Munnich A, Melki J. Identification and characterization of a spinal muscular atrophy-determining gene. Cell 1995; 80: 155-165
7. Wood-Allum C, Shaw PJ. Motor neurone disease: a practical update on diagnosis and management. Clin Med 2010; 10: 252-258
8. Logroscino G, Traynor BJ, Hardiman O, Chiò A, Mitchell D, Swingler RJ, Millul A, Benn E, Beghi E, EURALS. Incidence of amyotrophic lateral sclerosis in Europe. J Neurol Neurosurg Psychiatry 2010; 81: 385-390
9. Cooper-Knock J, Kirby J, Ferraiuolo L, Heath PR, Rattray M, Shaw PJ. Gene expression profiling in human neurodegenerative disease. Nat Rev Neurol 2012; 8: 518-530
10. Ling S-C, Polymenidou M, Cleveland DW. Converging mechanisms in ALS and FTD: disrupted RNA and protein homeostasis. Neuron 2013; 79: 416-438
11. Renton AE, Chiò A, Traynor BJ. State of play in amyotrophic lateral sclerosis genetics. Nat Neurosci 2014; 17: 17-23
12. Malik S, Roeder RG. The metazoan mediator co-activator complex as an integrative hub for transcriptional regulation. Nature 2010; 11: 761-772
13. Rodríguez-Navarro S, Hurt E. Linking gene regulation to mRNA production and export. Curr Opin Cell Biol 2011; 23: 302-309
14. van Hoof A, Wagner EJ. A brief survey of mRNA surveillance. Trends Biochem Sci 2011; 36: 585-592
15. Kwak J, Workman JL, Lee D. The proteasome and its regulatory roles in gene expression. Biochim Biophys Acta 2011; 1809: 88-96
16. Dreyfuss G, Matunis MJ, Piñol-Roma S, Burd CG. hnRNP proteins and the biogenesis of mRNA. Annu Rev Biochem 1993; 62: 289-321
17. Hieronymus H, Silver PA. A systems view of mRNP biology. Genes Dev 2004; 18: 2845-2860
18. Cooper TA, Wan L, Dreyfuss G. RNA and disease. Cell 2009; 136: 777-793
19. Singh RK, Cooper TA. Pre-mRNA splicing in disease and therapeutics. Trends Mol Med 2012; 18: 472-482
20. Le Quesne JPC, Spriggs KA, Bushell M, Willis AE. Dysregulation of protein synthesis and disease. J Pathol 2010; 220: 140-151
21. Maniatis T, Reed R. An extensive network of coupling among gene expression machines. Nature 2002; 416: 499-506
22. Luna R, Gaillard H, González-Aguilera C, Aguilera A. Biogenesis of mRNPs: integrating different processes in the eukaryotic nucleus. Chromosoma 2008; 117: 319-331
23. Hsin J-P, Manley JL. The RNA polymerase II CTD coordinates transcription and RNA processing. Genes Dev 2012; 26: 2119-2137
24. Jurado AR, Tan D, Jiao X, Kiledjian M, Tong L. Structure and function of pre-mRNA 5′-end capping quality control and 3′-end processing. Biochemistry 2014; 53: 1882-1898
25. Will CL. Lührmann R. Spliceosome structure and function. Cold Spring Harb Perspect Biol 2011; 3: a003707
26. Tian B, Manley JL. Alternative cleavage and polyadenylation: the long and short of it. Trends Biochem Sci 2013; 38: 312-320
27. Elkon R, Ugalde AP, Agami R. Alternative cleavage and polyadenylation: extent, regulation and function. Nature 2013; 14: 496-506
28. Walsh MJ, Hautbergue GM, Wilson SA. Structure and function of mRNA export adaptors. Biochem Soc Trans 2010; 38: 232-236
29. Müller-McNicoll M, Neugebauer KM. How cells get the message: dynamic assembly and function of mRNA-protein complexes. Nature 2013; 14: 275-287
30. Natalizio BJ, Wente SR. Postage for the messenger: designating routes for nuclear mRNA export. Trends Cell Biol 2013; 23: 365-373
31. Yonath A. Large facilities and the evolving ribosome, the cellular machine for genetic-code translation. J R Soc Interface 2009; 6: S575-585
32. Moore PB, Steitz TA. The roles of RNA in the synthesis of protein. Cold Spring Harb Perspect Biol 2011; 3: a003780
33. Gomes C, Merianda TT, Lee SJ, Yoo S, Twiss JL. Molecular determinants of the axonal mRNA transcriptome. Dev Neurobiol 2014; 74: 218-232
34. Nasir J, Floresco SB, O'Kusky JR, Diewert VM, Richman JM, Zeisler J, Borowski A, Marth JD, Phillips AG, Hayden MR. Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes. Cell 1995; 81: 811-823
35. Sathasivam K, Neueder A, Gipson TA, Landles C, Benjamin AC, Bondulich MK, Smith DL, Faull RLM, Roos RAC, Howland D, Detloff PJ, Housman DE, Bates GP. Aberrant splicing of HTT generates the pathogenic exon 1 protein in Huntington disease. Proc Natl Acad Sci USA 2013; 110: 2366-2370
36. Cornett J, Cao F, Wang C-E, Ross CA, Bates GP, Li S-H, Li X-J. Polyglutamine expansion of huntingtin impairs its nuclear export. Nat Genet 2005; 37: 198-204
37. DiFiglia M, Sapp E, Chase KO, Davies SW, Bates GP, Vonsattel JP, Aronin N. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 1997; 277: 1990-1993
38. Davies SW, Turmaine M, Cozens BA, DiFiglia M, Sharp AH, Ross CA, Scherzinger E, Wanker EE, Mangiarini L, Bates GP. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 1997; 90: 537-548
39. Tomás-Zapico C, Díez-Zaera M, Ferrer I, Gómez-Ramos P, Morán MA, Miras-Portugal MT, Díaz-Hernández M, Lucas JJ. α-Synuclein accumulates in huntingtin inclusions but forms independent filaments and its deficiency attenuates early phenotype in a mouse model of Huntington's disease. Hum Mol Genet 2012; 21: 495-510
40. Arrasate M, Mitra S, Schweitzer ES, Segal MR, Finkbeiner S. Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature 2004; 431: 805-810
41. Moumné L, Betuing S, Caboche J. Multiple aspects of gene dysregulation in Huntington's disease. Front Neurol 2013; 4: 127
42. Hodges A, Strand AD, Aragaki AK, Kuhn A, Sengstag T, Hughes G, Elliston LA, Hartog C, Goldstein DR, Thu D, Hollingsworth ZR, Collin F, Synek B, Holmans PA, Young AB, Wexler NS, Delorenzi M, Kooperberg C, Augood SJ, Faull RLM, Olson JM, Jones L, Luthi-Carter R. Regional and cellular gene expression changes in human Huntington's disease brain. Hum Mol Genet 2006; 15: 965-977
43. Anderson AN, Roncaroli F, Hodges A, Deprez M, Turkheimer FE. Chromosomal profiles of gene expression in Huntington's disease. Brain 2008; 131: 381-388
44. Becanovic K, Pouladi MA, Lim RS, Kuhn A, Pavlidis P, Luthi-Carter R, Hayden MR, Leavitt BR. Transcriptional changes in Huntington disease identified using genome-wide expression profiling and cross-platform analysis. Hum Mol Genet 2010; 19: 1438-1452
45. Cattaneo E, Zuccato C, Tartari M. Normal huntingtin function: an alternative approach to Huntington's disease. Nat Rev Neurosci 2005; 6: 919-930
46. Krzyzosiak WJ, Sobczak K, Wojciechowska M, Fiszer A, Mykowska A, Kozlowski P. Triplet repeat RNA structure and its role as pathogenic agent and therapeutic target. Nucleic Acids Res 2012; 40: 11-26
47. Tsoi H, Chan HYE. Expression of expanded CAG transcripts triggers nucleolar stress in Huntington's disease. Cerebellum 2013; 12: 310-312
48. Bañez-Coronel M, Porta S, Kagerbauer B, Mateu-Huertas E, Pantano L, Ferrer I, Guzmán M, Estivill X, Martí E. A pathogenic mechanism in Huntington's disease involves small CAG-repeated RNAs with neurotoxic activity. PLoS Genet 2012; 8: e1002481
49. Goehler H, Lalowski M, Stelzl U, Waelter S, Stroedicke M, Worm U, Droege A, Lindenberg KS, Knoblich M, Haenig C, Herbst M, Suopanki J, Scherzinger E, Abraham C, Bauer B, Hasenbank R, Fritzsche A, Ludewig AH, Büssow K, Buessow K, Coleman SH, Gutekunst C-A, Landwehrmeyer BG, Lehrach H, Wanker EE. A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease. Mol Cell 2004; 15: 853-865
50. Leavitt BR, van Raamsdonk JM, Shehadeh J, Fernandes H, Murphy Z, Graham RK, Wellington CL, Raymond LA, Hayden MR. Wild-type huntingtin protects neurons from excitotoxicity. J Neurochem 2006; 96: 1121-1129
51. Godin JD, Colombo K, Molina-Calavita M, Keryer G, Zala D, Charrin BC, Dietrich P, Volvert M-L, Guillemot F, Dragatsis I, Bellaiche Y, Saudou F, Nguyen L, Humbert S. Huntingtin is required for mitotic spindle orientation and mammalian neurogenesis. Neuron 2010; 67: 392-406
52. Colin E, Zala D, Liot G, Rangone H, Borrell-Pagès M, Li X-J, Saudou F, Humbert S. Huntingtin phosphorylation acts as a molecular switch for anterograde/retrograde transport in neurons. EMBO J 2008; 27: 2124-2134
53. Savas JN, Makusky A, Ottosen S, Baillat D, Then F, Krainc D, Shiekhattar R, Markey SP, Tanese N. Huntington's disease protein contributes to RNA-mediated gene silencing through association with Argonaute and P bodies. Proc Natl Acad Sci USA 2008; 105: 10820-10825
54. Zuccato C, Tartari M, Crotti A, Goffredo D, Valenza M, Conti L, Cataudella T, Leavitt BR, Hayden MR, Timmusk T, Rigamonti D, Cattaneo E. Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes. Nat Genet 2003; 35: 76-83
55. Zuccato C, Ciammola A, Rigamonti D, Leavitt BR, Goffredo D, Conti L, MacDonald ME, Friedlander RM, Silani V, Hayden MR, Timmusk T, Sipione S, Cattaneo E. Loss of huntingtin-mediated BDNF gene transcription in Huntington's disease. Science 2001; 293: 493-498
56. Johnson R, Zuccato C, Belyaev ND, Guest DJ, Cattaneo E, Buckley NJ. A microRNA-based gene dysregulation pathway in Huntington's disease. Neurobiol Dis 2008; 29: 438-445
57. Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, Bartel DP, Linsley PS, Johnson JM. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 2005; 433: 769-773
58. Kosik KS. The neuronal microRNA system. Nat Rev Neurosci 2006; 7: 911-920
59. Li S-H, Li X-J. Huntingtin-protein interactions and the pathogenesis of Huntington's disease. Trends Genet 2004; 20: 146-154
60. Ratovitski T, Chighladze E, Arbez N, Boronina T, Herbrich S, Cole RN, Ross CA. Huntingtin protein interactions altered by polyglutamine expansion as determined by quantitative proteomic analysis. Cell Cycle 2012; 11: 2006-2021
61. Rubinsztein DC, Carmichael J. Huntington's disease: molecular basis of neurodegeneration. Expert Rev Mol Med 2003; 5: 1-21
62. Johri A, Chandra A, Beal MF. PGC-1α, mitochondrial dysfunction, and Huntington's disease. Free Radic Biol Med 2013; 62: 37-46
63. Ayala-Peña S. Role of oxidative DNA damage in mitochondrial dysfunction and Huntington's disease pathogenesis. Free Radic Biol Med 2013; 62: 102-110
64. Jonson I, Ougland R, Klungland A, Larsen E. Oxidative stress causes DNA triplet expansion in Huntington's disease mouse embryonic stem cells. Stem Cell Res 2013; 11: 1264-1271
65. Tsunemi T, Ashe TD, Morrison BE, Soriano KR, Au J, Roque RAV, Lazarowski ER, Damian VA, Masliah E, La Spada AR. PGC-1α rescues Huntington's disease proteotoxicity by preventing oxidative stress and promoting TFEB function. Sci Transl Med 2012; 4: 142ra97
66. Steffan JS, Bodai L, Pallos J, Poelman M, McCampbell A, Apostol BL, Kazantsev A, Schmidt E, Zhu YZ, Greenwald M, Kurokawa R, Housman DE, Jackson GR, Marsh JL, Thompson LM. Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature 2001; 413: 739-743
67. Martin E, Betuing S, Pages C, Cambon K, Auregan G, Deglon N, Roze E, Caboche J. Mitogen- and stress-activated protein kinase 1-induced neuroprotection in Huntington's disease: role on chromatin remodeling at the PGC-1-alpha promoter. Hum Mol Genet 2011; 20: 2422-2434
68. Kim M-O, Chawla P, Overland RP, Xia E, Sadri-Vakili G, Cha J-HJ. Altered histone monoubiquitylation mediated by mutant huntingtin induces transcriptional dysregulation. J Neurosci 2008; 28: 3947-3957
69. Lee J, Hwang YJ, Ryu H, Kowall NW, Ryu H. Nucleolar dysfunction in Huntington's disease. Biochim Biophys Acta 2014; 1842: 785-790
70. van de Warrenburg BPC, Sinke RJ, Verschuuren-Bemelmans CC, Scheffer H, Brunt ER, Ippel PF, Maat-Kievit JA, Dooijes D, Notermans NC, Lindhout D, Knoers NVAM, Kremer HPH. Spinocerebellar ataxias in the Netherlands: prevalence and age at onset variance analysis. Neurology 2002; 12: 702-708
71. Brusco A, Gellera C, Cagnoli C, Saluto A, Castucci A, Michielotto C, Fetoni V, Mariotti C, Migone N, Di Donato S, Taroni F. Molecular genetics of hereditary spinocerebellar ataxia: mutation analysis of spinocerebellar ataxia genes and CAG/CTG repeat expansion detection in 225 Italian families. Arch Neurol 2004; 61: 727-733
72. Craig K, Keers SM, Archibald K, Curtis A, Chinnery PF. Molecular epidemiology of spinocerebellar ataxia type 6. Ann Neurol 2004; 55: 752-755
73. Harding AE. Clinical features and classification of inherited ataxias. Adv Neurol 1993; 61: 1-14
74. Zoghbi HY, Orr HT. Glutamine repeats and neurodegeneration. Annu Rev Neurosci 2000; 23: 217-247
75. Dueñas AM, Goold R, Giunti P. Molecular pathogenesis of spinocerebellar ataxias. Brain 2006; 129: 1357-1370
76. Ross CA, Poirier MA. Protein aggregation and neurodegenerative disease. Nat Med 2004; 10: S10-17
77. Park Y, Hong S, Kim S-J, Kang S. Proteasome function is inhibited by polyglutamine-expanded ataxin-1, the SCA1 gene product. Mol Cells 2005; 19: 23-30
78. Matsuyama Z, Yanagisawa NK, Aoki Y, Black JL, Lennon VA, Mori Y, Imoto K, Inuzuka T. Polyglutamine repeats of spinocerebellar ataxia 6 impair the cell-death-preventing effect of CaV2.1 Ca2+ channel-loss-of-function cellular model of SCA6. Neurobiol Dis 2004; 17: 198-204
79. Shimohata T, Nakajima T, Yamada M, Uchida C, Onodera O, Naruse S, Kimura T, Koide R, Nozaki K, Sano Y, Ishiguro H, Sakoe K, Ooshima T, Sato A, Ikeuchi T, Oyake M, Sato T, Aoyagi Y, Hozumi I, Nagatsu T, Takiyama Y, Nishizawa M, Goto J, Kanazawa I, Davidson I, Tanese N, Takahashi H, Tsuji S. Expanded polyglutamine stretches interact with TAFII130, interfering with CREB-dependent transcription. Nat Genet 2000; 26: 29-36
80. Li F, Macfarlan T, Pittman RN, Chakravarti D. Ataxin-3 is a histone-binding protein with two independent transcriptional corepressor activities. J Biol Chem 2002; 277: 45004-45012
81. Tsai C-C, Kao H-Y, Mitzutani A, Banayo E, Rajan H, McKeown M, Evans RM. Ataxin 1, a SCA1 neurodegenerative disorder protein, is functionally linked to the silencing mediator of retinoid and thyroid hormone receptors. Proc Natl Acad Sci USA 2004; 101: 4047-4052
82. Wojciechowska M, Krzyzosiak WJ. Cellular toxicity of expanded RNA repeats: focus on RNA foci. Hum Mol Genet 2011; 20: 3811-3821
83. Lin X, Ashizawa T. Recent progress in spinocerebellar ataxia type-10 (SCA10). Cerebellum 2005; 4: 37-42
84. White MC, Gao R, Xu W, Mandal SM, Lim JG, Hazra TK, Wakamiya M, Edwards SF, Raskin S, Teive HAG, Zoghbi HY, Sarkar PS, Ashizawa T. Inactivation of hnRNP K by expanded intronic AUUCU repeat induces apoptosis via translocation of PKCdelta to mitochondria in spinocerebellar ataxia 10. PLoS Genet 2010; 6: e1000984
85. Sato N, Amino T, Kobayashi K, Asakawa S, Ishiguro T, Tsunemi T, Takahashi M, Matsuura T, Flanigan KM, Iwasaki S, Ishino F, Saito Y, Murayama S, Yoshida M, Hashizume Y, Takahashi Y, Tsuji S, Shimizu N, Toda T, Ishikawa K, Mizusawa H. Spinocerebellar ataxia type 31 is associated with 'inserted' penta-nucleotide repeats containing (TGGAA)n. Am J Hum Genet 2009; 85: 544-557
86. Ohta Y, Hayashi T, Nagai M, Okamoto M, Nagotani S, Nagano I, Ohmori N, Takehisa Y, Murakami T, Shoji M, Kamiya T, Abe K. Two cases of spinocerebellar ataxia accompanied by involvement of the skeletal motor neuron system and bulbar palsy. Intern Med 2007; 46: 751-755
87. Abe K, Ikeda Y, Kurata T, Ohta Y, Manabe Y, Okamoto M, Takamatsu K, Ohta T, Takao Y, Shiro Y, Shoji M, Kamiya T, Kobayashi H, Koizumi A. Cognitive and affective impairments of a novel SCA/MND crossroad mutation Asidan. Eur J Neurol 2012; 19: 1070-1078
88. Kobayashi H, Abe K, Matsuura T, Ikeda Y, Hitomi T, Akechi Y, Habu T, Liu W, Okuda H, Koizumi A. Expansion of intronic GGCCTG hexanucleotide repeat in NOP56 causes SCA36, a type of spinocerebellar ataxia accompanied by motor neuron involvement. Am J Hum Genet 2011; 89: 121-130
89. DeJesus-Hernandez M, Mackenzie IR, Boeve BF, Boxer AL, Baker M, Rutherford NJ, Nicholson AM, Finch NA, Flynn H, Adamson J, Kouri N, Wojtas A, Sengdy P, Hsiung G-YR, Karydas A, Seeley WW, Josephs KA, Coppola G, Geschwind DH, Wszolek ZK, Feldman H, Knopman DS, Petersen RC, Miller BL, Dickson DW, Boylan KB, Graff-Radford NR, Rademakers R. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 2011; 72: 245-256
90. Renton AE, Majounie E, Waite A, Simón-Sánchez J, Rollinson S, Gibbs JR, Schymick JC, Laaksovirta H, van Swieten JC, Myllykangas L, Kalimo H, Paetau A, Abramzon Y, Remes AM, Kaganovich A, Scholz SW, Duckworth J, Ding J, Harmer DW, Hernandez DG, Johnson JO, Mok K, Ryten M, Trabzuni D, Guerreiro RJ, Orrell RW, Neal J, Murray A, Pearson J, Jansen IE, Sondervan D, Seelaar H, Blake D, Young K, Halliwell N, Callister JB, Toulson G, Richardson A, Gerhard A, Snowden J, Mann D, Neary D, Nalls MA, 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, ITALSGEN Consortium, Heckerman D, Rogaeva E, Zinman L, Rothstein JD, Sendtner M, Drepper C, Eichler EE, Alkan C, Abdullaev Z, Pack SD, Dutra A, Pak E, Hardy J, Singleton A, Williams NM, Heutink P, Pickering-Brown S, Morris HR, Tienari PJ, Traynor BJ. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 2011; 72: 257-268
91. Lee Y-B, Chen H-J, Peres JN, Gomez-Deza J, Attig J, Štalekar M, Troakes C, Nishimura AL, Scotter EL, Vance C, Adachi Y, Sardone V, Miller JW, Smith BN, Gallo J-M, Ule J, Hirth F, Rogelj B, Houart C, Shaw CE. Hexanucleotide repeats in ALS/FTD form length-dependent RNA foci, sequester RNA binding proteins, and are neurotoxic. Cell Rep 2013; 5: 1178-1186
92. Cooper-Knock J, Walsh MJ, Higginbottom A, Highley JR, Dickman MJ, Edbauer D, Ince PG, Wharton SB, Wilson SA, Kirby J, Hautbergue GM, Shaw PJ. Sequestration of multiple RNA recognition motif-containing proteins by C9ORF72 repeat expansions. Brain 2014; 137: 2040-2051
93. Nalavade R, Griesche N, Ryan DP, Hildebrand S, Krauss S. Mechanisms of RNA-induced toxicity in CAG repeat disorders. Cell Death Dis 2013; 4: e752
94. Evers MM, Toonen LJA, van Roon-Mom WMC. Ataxin-3 protein and RNA toxicity in spinocerebellar ataxia type 3: current insights and emerging therapeutic strategies. Mol Neurobiol 2014; 49: 1513-1531
95. Moseley ML, Zu T, Ikeda Y, Gao W, Mosemiller AK, Daughters RS, Chen G, Weatherspoon MR, Clark HB, Ebner TJ, Day JW, Ranum LPW. Bidirectional expression of CUG and CAG expansion transcripts and intranuclear polyglutamine inclusions in spinocerebellar ataxia type 8. Nat Genet 2006; 38: 758-769
96. Daughters RS, Tuttle DL, Gao W, Ikeda Y, Moseley ML, Ebner TJ, Swanson MS, Ranum LPW. RNA gain-of-function in spinocerebellar ataxia type 8. PLoS Genet 2009; 5: e1000600
97. Zu T, Gibbens B, Doty NS, Gomes-Pereira M, Huguet A, Stone MD, Margolis J, Peterson M, Markowski TW, Ingram MAC, Nan Z, Forster C, Low WC, Schoser B, Somia NV, Clark HB, Schmechel S, Bitterman PB, Gourdon G, Swanson MS, Moseley M, Ranum LPW. Non-ATG-initiated translation directed by microsatellite expansions. Proc Natl Acad Sci USA 2011; 108: 260-265
98. Cartegni L, Krainer AR. Disruption of an SF2/ASF-dependent exonic splicing enhancer in SMN2 causes spinal muscular atrophy in the absence of SMN1. Nat Genet 2002; 30: 377-384
99. Burnett BG, Muñoz E, Tandon A, Kwon DY, Sumner CJ, Fischbeck KH. Regulation of SMN protein stability. Mol Cell Biol 2009; 29: 1107-1115
100. Cho S, Dreyfuss G. A degron created by SMN2 exon 7 skipping is a principal contributor to spinal muscular atrophy severity. Genes Dev 2010; 24: 438-442
101. Ruggiu M, McGovern VL, Lotti F, Saieva L, Li DK, Kariya S, Monani UR, Burghes AHM, Pellizzoni L. A role for SMN exon 7 splicing in the selective vulnerability of motor neurons in spinal muscular atrophy. Mol Cell Biol 2012; 32: 126-138
102. Cho S, Moon H, Loh TJ, Oh HK, Williams DR, Liao DJ, Zhou J, Green MR, Zheng X, Shen H. PSF contacts exon 7 of SMN2 pre-mRNA to promote exon 7 inclusion. Biochim Biophys Acta 2014; 1839: 517-525
103. Cho S, Moon H, Loh TJ, Oh HK, Cho S, Choy HE, Song WK, Chun J-S, Zheng X, Shen H. hnRNP M facilitates exon 7 inclusion of SMN2 pre-mRNA in spinal muscular atrophy by targeting an enhancer on exon 7. Biochim Biophys Acta 2014; 1839: 306-315
104. Lorson CL, Hahnen E, Androphy EJ, Wirth B. A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proc Natl Acad Sci USA 1999; 96: 6307-6311
105. Monani UR, Lorson CL, Parsons DW, Prior TW, Androphy EJ, Burghes AH, McPherson JD. A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Hum Mol Genet 1999; 8: 1177-1183
106. Kashima T, Manley JL. A negative element in SMN2 exon 7 inhibits splicing in spinal muscular atrophy. Nat Genet 2003; 34: 460-463
107. Kashima T, Rao N, David CJ, Manley JL. hnRNP A1 functions with specificity in repression of SMN2 exon 7 splicing. Hum Mol Genet 2007; 16: 3149-3159
108. Pedrotti S, Bielli P, Paronetto MP, Ciccosanti F, Fimia GM, Stamm S, Manley JL, Sette C. The splicing regulator Sam68 binds to a novel exonic splicing silencer and functions in SMN2 alternative splicing in spinal muscular atrophy. EMBO J 2010; 29: 1235-1247
109. Chen H-H, Chang J-G, Lu R-M, Peng T-Y, Tarn W-Y. The RNA binding protein hnRNP Q modulates the utilization of exon 7 in the survival motor neuron 2 (SMN2) gene. Mol Cell Biol 2008; 28: 6929-6938
110. Miyajima H, Miyaso H, Okumura M, Kurisu J, Imaizumi K. Identification of a cis-acting element for the regulation of SMN exon 7 splicing. J Biol Chem 2002; 277: 23271-23277
111. Hua Y, Vickers TA, Okunola HL, Bennett CF, Krainer AR. Antisense masking of an hnRNP A1/A2 intronic splicing silencer corrects SMN2 splicing in transgenic mice. Am J Hum Genet 2008; 82: 834-848
112. Kashima T, Rao N, Manley JL. An intronic element contributes to splicing repression in spinal muscular atrophy. Proc Natl Acad Sci USA 2007; 104: 3426-3431
113. Hofmann Y, Lorson CL, Stamm S, Androphy EJ, Wirth B. Htra2-beta 1 stimulates an exonic splicing enhancer and can restore full-length SMN expression to survival motor neuron 2 (SMN2). Proc Natl Acad Sci USA 2000; 9: 9618-9623
114. Young PJ, DiDonato CJ, Hu D, Kothary R, Androphy EJ, Lorson CL. SRp30c-dependent stimulation of survival motor neuron (SMN) exon 7 inclusion is facilitated by a direct interaction with hTra2 beta 1. Hum Mol Genet 2002; 11: 577-587
115. Hofmann Y, Wirth B. hnRNP-G promotes exon 7 inclusion of survival motor neuron (SMN) via direct interaction with Htra2-beta1. Hum Mol Genet 2002; 11: 2037-2049
116. Prior TW, Krainer AR, Hua Y, Swoboda KJ, Snyder PC, Bridgeman SJ, Burghes AHM, Kissel JT. A positive modifier of spinal muscular atrophy in the SMN2 gene. Am J Hum Genet 2009; 85: 408-413
117. Vezain M, Saugier-Veber P, Goina E, Touraine R, Manel V, Toutain A, Fehrenbach S, Frébourg T, Pagani F, Tosi M, Martins A. A rare SMN2 variant in a previously unrecognized composite splicing regulatory element induces exon 7 inclusion and reduces the clinical severity of spinal muscular atrophy. Hum Mutat 2010; 31: E1110-1125
118. Bebee TW, Dominguez CE, Samadzadeh-Tarighat S, Akehurst KL, Chandler DS. Hypoxia is a modifier of SMN2 splicing and disease severity in a severe SMA mouse model. Hum Mol Genet 2012; 21: 4301-4313
119. Kolb SJ, Battle DJ, Dreyfuss G. Molecular functions of the SMN complex. J Child Neurol 2007; 22: 990-994
120. Fischer U, Englbrecht C, Chari A. Biogenesis of spliceosomal small nuclear ribonucleoproteins. Wiley Interdiscip Rev RNA 2011; 2: 718-731
121. Tsuiji H, Iguchi Y, Furuya A, Kataoka A, Hatsuta H, Atsuta N, Tanaka F, Hashizume Y, Akatsu H, Murayama S, Sobue G, Yamanaka K. Spliceosome integrity is defective in the motor neuron diseases ALS and SMA. EMBO Mol Med 2013; 5: 221-234
122. Liu H, Shafey D, Moores JN, Kothary R. Neurodevelopmental consequences of Smn depletion in a mouse model of spinal muscular atrophy. J Neurosci Res 2010; 88: 111-122
123. Zhang Z, Lotti F, Dittmar K, Younis I, Wan L, Kasim M, Dreyfuss G. SMN deficiency causes tissue-specific perturbations in the repertoire of snRNAs and widespread defects in splicing. Cell 2008; 133: 585-600
124. Lotti F, Imlach WL, Saieva L, Beck ES, Hao LT, Li DK, Jiao W, Mentis GZ, Beattie CE, McCabe BD, Pellizzoni L. An SMN-dependent U12 splicing event essential for motor circuit function. Cell 2012; 151: 440-454
125. See K, Yadav P, Giegerich M, Cheong PS, Graf M, Vyas H, Lee SGP, Mathavan S, Fischer U, Sendtner M, Winkler C. SMN deficiency alters Nrxn2 expression and splicing in zebrafish and mouse models of spinal muscular atrophy. Hum Mol Genet 2014; 23: 1754-1770
126. Fallini C, Bassell GJ, Rossoll W. Spinal muscular atrophy: the role of SMN in axonal mRNA regulation. Brain Res 2012; 1462: 81-92
127. Rossoll W, Jablonka S, Andreassi C, Kröning A-K, Karle K, Monani UR, Sendtner M. Smn, the spinal muscular atrophy-determining gene product, modulates axon growth and localization of beta-actin mRNA in growth cones of motoneurons. J Cell Biol 2003; 163: 801-812
128. Akten B, Kye MJ, Hao LT, Wertz MH, Singh S, Nie D, Huang J, Merianda TT, Twiss JL, Beattie CE, Steen JAJ, Sahin M. Interaction of survival of motor neuron (SMN) and HuD proteins with mRNA cpg15 rescues motor neuron axonal deficits. Proc Natl Acad Sci USA 2011; 108: 10337-10342
129. Rage F, Boulisfane N, Rihan K, Neel H, Gostan T, Bertrand E, Bordonné R, Soret J. Genome-wide identification of mRNAs associated with the protein SMN whose depletion decreases their axonal localization. RNA 2013; 19: 1755-1766
130. Sabra M, Texier P, Maalouf El J, Lomonte P. The Tudor protein survival motor neuron (SMN) is a chromatin-binding protein that interacts with methylated lysine 79 of histone H3. J Cell Sci 2013; 126: 3664-3677
131. Haramati S, Chapnik E, Sztainberg Y, Eilam R, Zwang R, Gershoni N, McGlinn E, Heiser PW, Wills A-M, Wirguin I, Rubin LL, Misawa H, Tabin CJ, Brown R, Chen A, Hornstein E. miRNA malfunction causes spinal motor neuron disease. Proc Natl Acad Sci USA 2010; 107: 13111-13116
132. Helmken C, Hofmann Y, Schoenen F, Oprea G, Raschke H, Rudnik-Schöneborn S, Zerres K, Wirth B. Evidence for a modifying pathway in SMA discordant families: reduced SMN level decreases the amount of its interacting partners and Htra2-beta1. Hum Genet 2003; 114: 11-21
133. Jodelka FM, Ebert AD, Duelli DM, Hastings ML. A feedback loop regulates splicing of the spinal muscular atrophy-modifying gene, SMN2. Hum Mol Genet 2010; 19: 4906-4917
134. Ferraiuolo L, Kirby J, Grierson AJ, Sendtner M, Shaw PJ. Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis. Nat Rev Neurol 2011; 7: 616-630
135. Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T, Grossman M, Clark CM. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 2006; 314: 130-133
136. Arai T, Hasegawa M, Akiyama H, Ikeda K, Nonaka T, Mori H, Mann D, Tsuchiya K, Yoshida M, Hashizume Y, Oda T. TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun 2006; 351: 602-611
137. Ince PG, Highley JR, Kirby J, Wharton SB, Takahashi H, Strong MJ, Shaw PJ. Molecular pathology and genetic advances in amyotrophic lateral sclerosis: an emerging molecular pathway and the significance of glial pathology. Acta Neuropathol 2011; 122: 657-671
138. Ihara R, Matsukawa K, Nagata Y, Kunugi H, Tsuji S, Chihara T, Kuranaga E, Miura M, Wakabayashi T, Hashimoto T, Iwatsubo T. RNA binding mediates neurotoxicity in the transgenic Drosophila model of TDP-43 proteinopathy. Hum Mol Genet 2013; 22: 4474-4484
139. Brockington A, Ning K, Heath PR, Wood E, Kirby J, Fusi N, Lawrence N, Wharton SB, Ince PG, Shaw PJ. Unravelling the enigma of selective vulnerability in neurodegeneration: motor neurons resistant to degeneration in ALS show distinct gene expression characteristics and decreased susceptibility to excitotoxicity. Acta Neuropathol 2013; 125: 95-109
140. Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 2006; 443: 787-795
141. Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J, O'Regan JP, Deng HX. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 1993; 362: 59-62
142. Gaudette M, Hirano M, Siddique T. Current status of SOD1 mutations in familial amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 2000; 1: 83-89
143. Sreedharan J, Blair IP, Tripathi VB, Hu X, Vance C, Rogelj B, Ackerley S, Durnall JC, Williams KL, Buratti E, Baralle F, de Belleroche J, Mitchell JD, Leigh PN, Al-Chalabi A, Miller CC, Nicholson G, Shaw CE. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 2008; 319: 1668-1672
144. Kwiatkowski TJ, Bosco DA, Leclerc AL, Tamrazian E, Vanderburg CR, Russ C, Davis A, Gilchrist J, Kasarskis EJ, Munsat T, Valdmanis P, Rouleau GA, Hosler BA, Cortelli P, de Jong PJ, Yoshinaga Y, Haines JL, Pericak-Vance MA, Yan J, Ticozzi N, Siddique T, McKenna-Yasek D, Sapp PC, Horvitz HR, Landers JE, Brown RH. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 2009; 323: 1205-1208
145. Vance C, Rogelj B, Hortobágyi T, De Vos KJ, Nishimura AL, Sreedharan J, Hu X, Smith B, Ruddy D, Wright P. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 2009; 323: 1208-1211
146. Mackenzie IRA, Rademakers R, Neumann M. TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia. Lancet Neurol 2010; 9: 995-1007
147. Zhang D, Iyer LM, He F, Aravind L. Discovery of novel DENN proteins: implications for the evolution of eukaryotic intracellular membrane structures and human disease. Front Genet 2012; 3: 283
148. Stewart H, Rutherford NJ, Briemberg H, Krieger C, Cashman N, Fabros M, Baker M, Fok A, DeJesus-Hernandez M, Eisen A, Rademakers R, Mackenzie IRA. Clinical and pathological features of amyotrophic lateral sclerosis caused by mutation in the C9ORF72 gene on chromosome 9p. Acta Neuropathol 2012; 123: 409-417
149. Cooper-Knock J, Hewitt C, Highley JR, Brockington A, Milano A, Man S, Martindale J, Hartley J, Walsh T, Gelsthorpe C, Baxter L, Forster G, Fox M, Bury J, Mok K, McDermott CJ, Traynor BJ, Kirby J, Wharton SB, Ince PG, Hardy J, Shaw PJ. Clinico-pathological features in amyotrophic lateral sclerosis with expansions in C9ORF72. Brain 2012; 135: 751-764
150. Fratta P, Mizielinska S, Nicoll AJ, Zloh M, Fisher EMC, Parkinson G, Isaacs AM. C9orf72 hexanucleotide repeat associated with amyotrophic lateral sclerosis and frontotemporal dementia forms RNA G-quadruplexes. Sci Rep 2012; 2: 1016
151. Reddy K, Zamiri B, Stanley SYR, Macgregor RB, Pearson CE. 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 2013; 288: 9860-9866
152. Haeusler AR, Donnelly CJ, Periz G, Simko EAJ, Shaw PG, Kim M-S, Maragakis NJ, Troncoso JC, Pandey A, Sattler R, Rothstein JD, Wang J. C9orf72 nucleotide repeat structures initiate molecular cascades of disease. Nature 2014; 507: 195-200
153. Donnelly CJ, Zhang P-W, Pham JT, Heusler AR, Mistry NA, Vidensky S, Daley EL, Poth EM, Hoover B, Fines DM, Maragakis N, Tienari PJ, Petrucelli L, Traynor BJ, Wang J, Rigo F, Bennett CF, Blackshaw S, Sattler R, Rothstein JD. RNA toxicity from the ALS/FTD C9ORF72 expansion is mitigated by antisense intervention. Neuron 2013; 80: 415-428
154. Sareen D, O'Rourke JG, Meera P, Muhammad AKMG, Grant S, Simpkinson M, Bell S, Carmona S, Ornelas L, Sahabian A, Gendron T, Petrucelli L, Baughn M, Ravits J, Harms MB, Rigo F, Bennett CF, Otis TS, Svendsen CN, Baloh RH. Targeting RNA foci in iPSC-derived motor neurons from ALS patients with a C9ORF72 repeat expansion. Sci Transl Med 2013; 5: 208ra149
155. Lagier-Tourenne C, Baughn M, Rigo F, Sun S, Liu P, Li H-R, Jiang J, Watt AT, Chun S, Katz M, Qiu J, Sun Y, Ling S-C, Zhu Q, Polymenidou M, Drenner K, Artates JW, McAlonis-Downes M, Markmiller S, Hutt KR, Pizzo DP, Cady J, Harms MB, Baloh RH, Vandenberg SR, Yeo GW, Fu X-D, Bennett CF, Cleveland DW, Ravits J. Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration. Proc Natl Acad Sci USA 2013; 110: E4530-4539
156. Zu T, Liu Y, Bañez-Coronel M, Reid T, Pletnikova O, Lewis J, Miller TM, Harms MB, Falchook AE, Subramony SH, Ostrow LW, Rothstein JD, Troncoso JC, Ranum LPW. RAN proteins and RNA foci from antisense transcripts in C9ORF72 ALS and frontotemporal dementia. Proc Natl Acad Sci USA 2013; 110: E4968-4977
157. Mizielinska S, Lashley T, Norona FE, Clayton EL, Ridler CE, Fratta P, Isaacs AM. C9orf72 frontotemporal lobar degeneration is characterised by frequent neuronal sense and antisense RNA foci. Acta Neuropathol 2013; 126: 845-857
158. Gijselinck I, Van Langenhove T, van der Zee J, Sleegers K, Philtjens S, Kleinberger G, Janssens J, Bettens K, Van Cauwenberghe C, Pereson S, Engelborghs S, Sieben A, De Jonghe P, Vandenberghe R, Santens P, De Bleecker J, Maes G, Bäumer V, Dillen L, Joris G, Cuijt I, Corsmit E, Elinck E, Van Dongen J, Vermeulen S, Van den Broeck M, Vaerenberg C, Mattheijssens M, Peeters K, Robberecht W, Cras P, Martin J-J, De Deyn PP, Cruts MR, Van Broeckhoven C. A C9orf72 promoter repeat expansion in a Flanders-Belgian cohort with disorders of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum: a gene identification study. Lancet Neurol 2012; 1: 54-65
159. Belzil VV, Bauer PO, Prudencio M, Gendron TF, Stetler CT, Yan IK, Pregent L, Daughrity L, Baker MC, Rademakers R, Boylan K, Patel TC, Dickson DW, Petrucelli L. Reduced C9orf72 gene expression in c9FTD/ALS is caused by histone trimethylation, an epigenetic event detectable in blood. Acta Neuropathol 2013; 126: 895-905
160. Ciura S, Lattante S, Le Ber I, Latouche M, Tostivint H, Brice A, Kabashi E. Loss of function of C9orf72 causes motor deficits in a zebrafish model of Amyotrophic Lateral Sclerosis. Ann Neurol 2013; 74: 180-187
161. Xi Z, Zinman L, Moreno D, Schymick J, Liang Y, Sato C, Zheng Y, Ghani M, Dib S, Keith J, Robertson J, Rogaeva E. Hypermethylation of the CpG island near the G4C2 repeat in ALS with a C9orf72 expansion. Am J Hum Genet 2013; 92: 981-989
162. Waite AJ, Bäumer D, East S, Neal J, Morris HR, Ansorge O, Blake DJ. Reduced C9orf72 protein levels in frontal cortex of amyotrophic lateral sclerosis and frontotemporal degeneration brain with the C9ORF72 hexanucleotide repeat expansion. Neurobiol Aging 2014; 35: 1779
163. Mori K, Lammich S, Mackenzie IRA, Forné I, Zilow S, Kretzschmar H, Edbauer D, Janssens J, Kleinberger G, Cruts MR, Herms J, Neumann M, Van Broeckhoven C, Arzberger T, Haass C. 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 2013; 125: 413-423
164. Xu Z, Poidevin M, Li X, Li Y, Shu L, Nelson DL, Li H, Hales CM, Gearing M, Wingo TS. Expanded GGGGCC repeat RNA associated with amyotrophic lateral sclerosis and frontotemporal dementia causes neurodegeneration. Proc Natl Acad Sci USA 2013; 110: 7778-7783
165. Ash PEA, Bieniek KF, Gendron TF, Caulfield T, Lin W-L, DeJesus-Hernandez M, van Blitterswijk MM, Jansen-West K, Paul JW, Rademakers R, Boylan KB, Dickson DW, Petrucelli L. Unconventional translation of C9ORF72 GGGGCC expansion generates insoluble polypeptides specific to c9FTD/ALS. Neuron 2013; 77: 639-646
166. Mori K, Weng S-M, Arzberger T, May S, Rentzsch K, Kremmer E, Schmid B, Kretzschmar HA, Cruts MR, Van Broeckhoven C, Haass C, Edbauer D. The C9orf72 GGGGCC repeat is translated into aggregating dipeptide-repeat proteins in FTLD/ALS. Science 2013; 339: 1335-1338
167. Cooper-Knock J, Higginbottom A, Connor-Robson N, Bayatti N, Bury JJ, Kirby J, Ninkina N, Buchman VL, Shaw PJ. C9ORF72 transcription in a frontotemporal dementia case with two expanded alleles. Neurology 2013; 81: 1719-1721
168. Harms MB, Cady J, Zaidman C, Cooper P, Bali T, Allred P, Cruchaga C, Baughn M, Libby RT, Pestronk A, Goate A, Ravits J, Baloh RH. Lack of C9ORF72 coding mutations supports a gain of function for repeat expansions in amyotrophic lateral sclerosis. Neurobiol Aging 2013; 34: 2234
169. Kwon I, Xiang S, Kato M, Wu L, Theodoropoulos P, Wang T, Kim J, Yun J, Xie Y, McKnight SL. Poly-dipeptides encoded by the C9ORF72 repeats bind nucleoli, impede RNA biogenesis, and kill cells. Science 2014; 345: 1139-1145
170. Mizielinska S, Grönke S, Niccoli T, Ridler CE, Clayton EL, Devoy A, Moens T, Norona FE, Woollacott IOC, Pietrzyk J, Cleverley K, Nicoll AJ, Pickering-Brown S, Dols J, Cabecinha M, Hendrich O, Fratta P, Fisher EMC, Partridge L, Isaacs AM. C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins. Science 2014; 345: 1192-1194
171. Barber SC, Mead RJ, Shaw PJ. Oxidative stress in ALS: a mechanism of neurodegeneration and a therapeutic target. Biochim Biophys Acta 2006; 1762: 1051-1067
172. Kirby J, Ning K, Ferraiuolo L, Heath PR, Ismail A, Kuo S-W, Valori CF, Cox L, Sharrack B, Wharton SB, Ince PG, Shaw PJ, Azzouz M. Phosphatase and tensin homologue/protein kinase B pathway linked to motor neuron survival in human superoxide dismutase 1-related amyotrophic lateral sclerosis. Brain 2011; 134: 506-517
173. Bruijn LI, Becher MW, Lee MK, Anderson KL, Jenkins NA, Copeland NG, Sisodia SS, Rothstein JD, Borchelt DR, Price DL, Cleveland DW. ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions. Neuron 1997; 18: 327-338
174. Bruijn LI, Houseweart MK, Kato S, Anderson KL, Anderson SD, Ohama E, Reaume AG, Scott RW, Cleveland DW. Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1. Science 1998; 281: 1851-1854
175. Honda D, Ishigaki S, Iguchi Y, Fujioka Y, Udagawa T, Masuda A, Ohno K, Katsuno M, Sobue G. The ALS/FTLD-related RNA-binding proteins TDP-43 and FUS have common downstream RNA targets in cortical neurons. FEBS Open Bio 2013; 4: 1-10
176. Nakaya T, Alexiou P, Maragkakis M, Chang A, Mourelatos Z. FUS regulates genes coding for RNA-binding proteins in neurons by binding to their highly conserved introns. RNA 2013; 19: 498-509
177. Yoshimura A, Fujii R, Watanabe Y, Okabe S, Fukui K, Takumi T. Myosin-Va facilitates the accumulation of mRNA/protein complex in dendritic spines. Curr Biol 2006; 16: 2345-2351
178. Kawahara Y, Mieda-Sato A. TDP-43 promotes microRNA biogenesis as a component of the Drosha and Dicer complexes. Proc Natl Acad Sci USA 2012; 109: 3347-3352
179. Morlando M, Dini Modigliani S, Torrelli G, Rosa A, Di Carlo V, Caffarelli E, Bozzoni I. FUS stimulates microRNA biogenesis by facilitating co-transcriptional Drosha recruitment. EMBO J 2012; 31: 4502-4510
180. Fiesel FC, Weber SS, Supper J, Zell A, Kahle PJ. TDP-43 regulates global translational yield by splicing of exon junction complex component SKAR. Nucleic Acids Res 2012; 40: 2668-2682
181. Higashi S, Kabuta T, Nagai Y, Tsuchiya Y, Akiyama H, Wada K. TDP-43 associates with stalled ribosomes and contributes to cell survival during cellular stress. J Neurochem 2013; 126: 288-300
182. Lagier-Tourenne C, Polymenidou M, Hutt KR, Vu AQ, Baughn M, Huelga SC, Clutario KM, Ling S-C, Liang TY, Mazur C, Wancewicz E, Kim AS, Watt A, Freier S, Hicks GG, Donohue JP, Shiue L, Bennett CF, Ravits J, Cleveland DW, Yeo GW. Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs. Nat Neurosci 2012; 15: 1488-1497
183. Rogelj B, Easton LE, Bogu GK, Stanton LW, Rot G, Curk T, Zupan B, Sugimoto Y, Modic M, Haberman N, Tollervey J, Fujii R, Takumi T, Shaw CE, Ule J. Widespread binding of FUS along nascent RNA regulates alternative splicing in the brain. Sci Rep 2012; 2: 603
184. Tollervey JR, Curk T, Rogelj B, Briese M, Cereda M, Kayikci M, König J, Hortobágyi T, Nishimura AL, Župunski V. Characterizing the RNA targets and position-dependent splicing regulation by TDP-43. Nat Neurosci 2011; 14: 452-458
185. Xiao S, Sanelli T, Dib S, Sheps D, Findlater J, Bilbao J, Keith J, Zinman L, Rogaeva E, Robertson J. RNA targets of TDP-43 identified by UV-CLIP are deregulated in ALS. Mol Cell Neurosci 2011; 47: 167-180
186. Arnold ES, Ling S-C, Huelga SC, Lagier-Tourenne C, Polymenidou M, Ditsworth D, Kordasiewicz HB, McAlonis-Downes M, Platoshyn O, Parone PA, Da Cruz S, Clutario KM, Swing D, Tessarollo L, Marsala M, Shaw CE, Yeo GW, Cleveland DW. ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43. Proc Natl Acad Sci USA 2013; 110: E736-745
187. Fujioka Y, Ishigaki S, Masuda A, Iguchi Y, Udagawa T, Watanabe H, Katsuno M, Ohno K, Sobue G. FUS-regulated region- and cell-type-specific transcriptome is associated with cell selectivity in ALS/FTLD. Sci Rep 2013; 3: 2388
188. Huang C, Huang B, Bi F, Yan LH, Tong J, Huang J, Xia X-G, Zhou H. Profiling the genes affected by pathogenic TDP-43 in astrocytes. J Neurochem 2014; 129: 932-939
189. Highley JR, Kirby J, Jansweijer JA, Webb PS, Hewamadduma CA, Heath PR, Higginbottom A, Raman R, Ferraiuolo L, Cooper-Knock J, McDermott CJ, Wharton SB, Shaw PJ, Ince PG. Loss of nuclear TDP-43 in ALS causes altered expression of splicing machinery and widespread dysregulation of RNA splicing in motor neurons. Neuropathol Appl Neurobiol 2014; 40: 670-685. doi: 10.1111/nan.12148
190. Mitchell JC, McGoldrick P, Vance C, Hortobágyi T, Sreedharan J, Rogelj B, Tudor EL, Smith BN, Klasen C, Miller CCJ, Cooper JD, Greensmith L, Shaw CE. Overexpression of human wild-type FUS causes progressive motor neuron degeneration in an age- and dose-dependent fashion. Acta Neuropathol 2013; 125: 273-288
191. Yamazaki T, Chen S, Yu Y, Yan B, Haertlein TC, Carrasco MA, Tapia JC, Zhai B, Das R, Lalancette-Hebert M, Sharma A, Chandran S, Sullivan G, Nishimura AL, Shaw CE, Gygi SP, Shneider NA, Maniatis T, Reed R. FUS-SMN protein interactions link the motor neuron diseases ALS and SMA. Cell Rep 2012; 2: 799-806
192. Shan X, Chiang P-M, Price DL, Wong PC. Altered distributions of Gemini of coiled bodies and mitochondria in motor neurons of TDP-43 transgenic mice. Proc Natl Acad Sci USA 2010; 107: 16325-16330
193. Ling SC, Albuquerque CP, Han JS, Lagier-Tourenne C, Tokunaga S, Zhou H, Cleveland DW. ALS-associated mutations in TDP-43 increase its stability and promote TDP-43 complexes with FUS/TLS. Proc Natl Acad Sci USA 2010; 107: 13318-13323
194. Wang I-F, Reddy NM, Shen C-KJ. Higher order arrangement of the eukaryotic nuclear bodies. Proc Natl Acad Sci USA 2002; 99: 13583-13588
195. Buratti E, Brindisi A, Giombi M, Tisminetzky S, Ayala YM, Baralle FE. TDP-43 binds heterogeneous nuclear ribonucleoprotein A/B through its C-terminal tail: an important region for the inhibition of cystic fibrosis transmembrane conductance regulator exon 9 splicing. J Biol Chem 2005; 280: 37572-37584
196. Lagier-Tourenne C, Cleveland DW. Rethinking ALS: the FUS about TDP-43. Cell 2009; 136: 1001-1004
197. Lattante S, Rouleau GA, Kabashi E. TARDBP and FUS mutations associated with amyotrophic lateral sclerosis: summary and update. Hum Mutat 2013; 34: 812-826
198. Barmada SJ, Skibinski G, Korb E, Rao EJ, Wu JY, Finkbeiner S. Cytoplasmic mislocalization of TDP-43 is toxic to neurons and enhanced by a mutation associated with familial amyotrophic lateral sclerosis. J Neurosci 2010; 30: 639-649
199. Kabashi E, Lin L, Tradewell ML, Dion PA, Bercier V, Bourgouin P, Rochefort D, Bel Hadj S, Durham HD, Vande Velde C, Rouleau GA, Drapeau P. Gain and loss of function of ALS-related mutations of TARDBP (TDP-43) cause motor deficits in vivo. Hum Mol Genet 2010; 19: 671-683
200. Alami NH, Smith RB, Carrasco MA, Williams LA, Winborn CS, Han SSW, Kiskinis E, Winborn B, Freibaum BD, Kanagaraj A, Clare AJ, Badders NM, Bilican B, Chaum E, Chandran S, Shaw CE, Eggan KC, Maniatis T, Taylor JP. Axonal transport of TDP-43 mRNA granules is impaired by ALS-causing mutations. Neuron 2014; 81: 536-543
201. Chen Y-Z, Bennett CL, Huynh HM, Blair IP, Puls I, Irobi J, Dierick I, Abel A, Kennerson ML, Rabin BA, Nicholson GA, Auer-Grumbach M, Wagner K, De Jonghe P, Griffin JW, Fischbeck KH, Timmerman V, Cornblath DR, Chance PF. DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4). Am J Hum Genet 2004; 74: 1128-1135
202. Greenway MJ, Alexander MD, Ennis S, Traynor BJ, Corr B, Frost E, Green A, Hardiman O. A novel candidate region for ALS on chromosome 14q11.2. Neurology 2004; 63: 1936-1938
203. Greenway MJ, Andersen PM, Russ C, Ennis S, Cashman S, Donaghy C, Patterson V, Swingler R, Kieran D, Prehn J, Morrison KE, Green A, Acharya KR, Brown RH, Hardiman O. ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis. Nat Genet 2006; 38: 411-413
204. Simpson CL, Lemmens R, Miskiewicz K, Broom WJ, Hansen VK, van Vught PWJ, Landers JE, Sapp P, Van Den Bosch L, Knight J, Neale BM, Turner MR, Veldink JH, Ophoff RA, Tripathi VB, Beleza A, Shah MN, Proitsi P, Van Hoecke A, Carmeliet P, Horvitz HR, Leigh PN, Shaw CE, van den Berg LH, Sham PC, Powell JF, Verstreken P, Brown RH, Robberecht W, Al-Chalabi A. Variants of the elongator protein 3 (ELP3) gene are associated with motor neuron degeneration. Hum Mol Genet 2009; 18: 472-481
205. Couthouis J, Hart MP, Shorter J, DeJesus-Hernandez M, Erion R, Oristano R, Liu AX, Ramos D, Jethava N, Hosangadi D, Epstein J, Chiang A, Diaz Z, Nakaya T, Ibrahim F, Kim H-J, Solski JA, Williams KL, Mojsilovic-Petrovic J, Ingre C, Boylan K, Graff-Radford NR, Dickson DW, Clay-Falcone D, Elman L, McCluskey L, Greene R, Kalb RG, Lee VMY, Trojanowski JQ, Ludolph A, Robberecht W, Andersen PM, Nicholson GA, Blair IP, King OD, Bonini NM, Van Deerlin V, Rademakers R, Mourelatos Z, Gitler AD. A yeast functional screen predicts new candidate ALS disease genes. Proc Natl Acad Sci USA 2011; 108: 20881-20890
206. Ticozzi N, Vance C, Leclerc AL, Keagle P, Glass JD, McKenna-Yasek D, Sapp PC, Silani V, Bosco DA, Shaw CE, Brown RH, Landers JE. Mutational analysis reveals the FUS homolog TAF15 as a candidate gene for familial amyotrophic lateral sclerosis. Am J Med Genet B Neuropsychiatr Genet 2011; 156B: 285-290
207. Couthouis J, Hart MP, Erion R, King OD, Diaz Z, Nakaya T, Ibrahim F, Kim H-J, Mojsilovic-Petrovic J, Panossian S, Kim CE, Frackelton EC, Solski JA, Williams KL, Clay-Falcone D, Elman L, McCluskey L, Greene R, Hakonarson H, Kalb RG, Lee VMY, Trojanowski JQ, Nicholson GA, Blair IP, Bonini NM, Van Deerlin VM, Mourelatos Z, Shorter J, Gitler AD. Evaluating the role of the FUS/TLS-related gene EWSR1 in amyotrophic lateral sclerosis. Hum Mol Genet 2012; 21: 2899-2911
208. Lim C, Allada R. ATAXIN-2 activates PERIOD translation to sustain circadian rhythms in Drosophila. Science 2013; 340: 875-879
209. Zhang Y, Ling J, Yuan C, Dubruille R, Emery P. A role for Drosophila ATX2 in activation of PER translation and circadian behavior. Science 2013; 340: 879-882
210. Elden AC, Kim H-J, Hart MP, Chen-Plotkin AS, Johnson BS, Fang X, Armakola M, Geser F, Greene R, Lu MM, Padmanabhan A, Clay-Falcone D, McCluskey L, Elman L, Juhr D, Gruber PJ, Rüb U, Auburger G, Trojanowski JQ, Lee VMY, Van Deerlin VM, Bonini NM, Gitler AD. Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature 2010; 466: 1069-1075
211. Kim H-J, Raphael AR, LaDow ES, McGurk L, Weber RA, Trojanowski JQ, Lee VMY, Finkbeiner S, Gitler AD, Bonini NM. Therapeutic modulation of eIF2α phosphorylation rescues TDP-43 toxicity in amyotrophic lateral sclerosis disease models. Nat Genet 2014; 46: 152-160
212. Johnson JO, Pioro EP, Boehringer A, Chia R, Feit H, Renton AE, Pliner HA, Abramzon Y, Marangi G, Winborn BJ, Gibbs JR, Nalls MA, Morgan S, Shoai M, Hardy J, Pittman A, Orrell RW, Malaspina A, Sidle KC, Fratta P, Harms MB, Baloh RH, Pestronk A, Weihl CC, Rogaeva E, Zinman L, Drory VE, Borghero G, Mora G, Calvo A, Rothstein JD, ITALSGEN, Drepper C, Sendtner M, Singleton AB, Taylor JP, Cookson MR, Restagno G, Sabatelli M, Bowser R, Chiò A, Traynor BJ. Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis. Nat Neurosci 2014; 17: 664-666
213. Kim HJ, Kim NC, Wang Y-D, Scarborough EA, Moore J, Diaz Z, MacLea KS, Freibaum B, Li S, Molliex A, Kanagaraj AP, Carter R, Boylan KB, Wojtas AM, Rademakers R, Pinkus JL, Greenberg SA, Trojanowski JQ, Traynor BJ, Smith BN, Topp S, Gkazi A-S, Miller J, Shaw CE, Kottlors M, Kirschner J, Pestronk A, Li YR, Ford AF, Gitler AD, Benatar M, King OD, Kimonis VE, Ross ED, Weihl CC, Shorter J, Taylor JP. Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature 2013; 495: 467-473
214. Valor LM. Transcription, epigenetics and ameliorative strategies in Huntington's disease: a genome-wide perspective. Mol Neurobiol 2014. doi: 10.1007/s12035-014-8715-8
215. Bettencourt C, Ryten M, Forabosco P, Schorge S, Hersheson J, Hardy J, Houlden H, United Kingdom Brain Expression Consortium. Insights from cerebellar transcriptomic analysis into the pathogenesis of ataxia. JAMA Neurol 2014; 71: 831-839
216. Wirth B, Garbes L, Riessland M. How genetic modifiers influence the phenotype of spinal muscular atrophy and suggest future therapeutic approaches. Curr Opin Genet Dev 2013; 23: 330-338
217. Tanaka F, Ikenaka K, Yamamoto M, Sobue G. Neuropathology and omics in motor neuron diseases. Neuropathology 2012; 32: 458-462
218. Jacobsen JC, Gregory GC, Woda JM, Thompson MN, Coser KR, Murthy V, Kohane IS, Gusella JF, Seong IS, MacDonald ME, Shioda T, Lee J-M. HD CAG-correlated gene expression changes support a simple dominant gain of function. Hum Mol Genet 2011; 20: 2846-2860
219. Feyeux M, Bourgois-Rocha F, Redfern A, Giles P, Lefort N, Aubert S, Bonnefond C, Bugi A, Ruiz M, Deglon N, Jones L, Peschanski M, Allen ND, Perrier AL. Early transcriptional changes linked to naturally occurring Huntington's disease mutations in neural derivatives of human embryonic stem cells. Hum Mol Genet 2012; 21: 3883-3895
220. HD iPSC Consortium. Induced pluripotent stem cells from patients with Huntington's disease show CAG-repeat-expansion-associated phenotypes. Cell Stem Cell 2012; 11: 264-278
221. Soldati C, Bithell A, Johnston C, Wong K-Y, Stanton LW, Buckley NJ. Dysregulation of REST-regulated coding and non-coding RNAs in a cellular model of Huntington's disease. J Neurochem 2013; 124: 418-430
222. Lewandowski NM, Bordelon Y, Brickman AM, Angulo S, Khan U, Muraskin J, Griffith EY, Wasserman P, Menalled L, Vonsattel JP, Marder K, Small SA, Moreno H. Regional vulnerability in Huntington's disease: fMRI-guided molecular analysis in patients and a mouse model of disease. Neurobiol Dis 2013; 52: 84-93
223. Lee J-M, Galkina EI, Levantovsky RM, Fossale E, Anne Anderson M, Gillis T, Srinidhi Mysore J, Coser KR, Shioda T, Zhang B, Furia MD, Derry J, Kohane IS, Seong IS, Wheeler VC, Gusella JF, MacDonald ME. Dominant effects of the Huntington's disease HTT CAG repeat length are captured in gene-expression data sets by a continuous analysis mathematical modeling strategy. Hum Mol Genet 2013; 22: 3227-3238
224. Chou A-H, Chen C-Y, Chen S-Y, Chen W-J, Chen Y-L, Weng Y-S, Wang H-L. Polyglutamine-expanded ataxin-7 causes cerebellar dysfunction by inducing transcriptional dysregulation. Neurochem Int 2010; 56: 329-339
225. Friedrich B, Euler P, Ziegler R, Kuhn A, Landwehrmeyer BG, Luthi-Carter R, Weiller C, Hellwig S, Zucker B. Comparative analyses of Purkinje cell gene expression profiles reveal shared molecular abnormalities in models of different polyglutamine diseases. Brain Res 2012; 1481: 37-48
226. Ren J, Jegga AG, Zhang M, Deng J, Liu J, Gordon CB, Aronow BJ, Lu LJ, Zhang B, Ma J. A Drosophila model of the neurodegenerative disease SCA17 reveals a role of RBP-J/Su(H) in modulating the pathological outcome. Hum Mol Genet 2011; 20: 3424-3436
227. Damrath E, Heck MV, Gispert S, Azizov M, Nowock J, Seifried C, Rüb U, Walter M, Auburger G. ATXN2-CAG42 sequesters PABPC1 into insolubility and induces FBXW8 in cerebellum of old ataxic knock-in mice. PLoS Genet 2012; 8: e1002920
228. Hsieh M, Chang W-H, Hsu C-F, Nishimori I, Kuo C-L, Minakuchi T. Altered expression of carbonic anhydrase-related protein XI in neuronal cells expressing mutant ataxin-3. Cerebellum 2013; 12: 338-349
229. Mancini C, Roncaglia P, Brussino A, Stevanin G, Buono Lo N, Krmac H, Maltecca F, Gazzano E, Bartoletti Stella A, Calvaruso MA, Iommarini L, Cagnoli C, Forlani S, Le Ber I, Durr A, Brice A, Ghigo D, Casari G, Porcelli AM, Funaro A, Gasparre G, Gustincich S, Brusco A. Genome-wide expression profiling and functional characterization of SCA28 lymphoblastoid cell lines reveal impairment in cell growth and activation of apoptotic pathways. BMC Med Genomics 2013; 6: 22
230. Garcia EL, Lu Z, Meers MP, Praveen K, Matera AG. Developmental arrest of Drosophila survival motor neuron (Smn) mutants accounts for differences in expression of minor intron-containing genes. RNA 2013; 19: 1510-1516
231. Graveley BR, Brooks AN, Carlson JW, Duff MO, Landolin JM, Yang L, Artieri CG, van Baren MJ, Boley N, Booth BW, Brown JB, Cherbas L, Davis CA, Dobin A, Li R, Lin W, Malone JH, Mattiuzzo NR, Miller D, Sturgill D, Tuch BB, Zaleski C, Zhang D, Blanchette M, Dudoit S, Eads B, Green RE, Hammonds A, Jiang L, Kapranov P, Langton L, Perrimon N, Sandler JE, Wan KH, Willingham A, Zhang Y, Zou Y, Andrews J, Bickel PJ, Brenner SE, Brent MR, Cherbas P, Gingeras TR, Hoskins RA, Kaufman TC, Oliver B, Celniker SE. The developmental transcriptome of Drosophila melanogaster. Nature 2011; 471: 473-479
232. Zhang Z, Pinto AM, Wan L, Wang W, Berg MG, Oliva I, Singh LN, Dengler C, Wei Z, Dreyfuss G. Dysregulation of synaptogenesis genes antecedes motor neuron pathology in spinal muscular atrophy. Proc Natl Acad Sci USA 2013; 110: 19348-19353
233. Mathavan S, Lee SGP, Mak A, Miller LD, Murthy KRK, Govindarajan KR, Tong Y, Wu YL, Lam SH, Yang H, Ruan Y, Korzh V, Gong Z, Liu ET, Lufkin T. Transcriptome analysis of zebrafish embryogenesis using microarrays. PLoS Genet 2005; 1: 260-276
234. Acsadi G, Li X, Murphy KJ, Swoboda KJ, Parker GC. Alpha-synuclein loss in spinal muscular atrophy. J Mol Neurosci 2011; 43: 275-283
235. Ismail A, Cooper-Knock J, Highley JR, Milano A, Kirby J, Goodall E, Lowe J, Scott I, Constantinescu CS, Walters SJ, Price S, McDermott CJ, Sawcer S, Compston DAS, Sharrack B, Shaw PJ. Concurrence of multiple sclerosis and amyotrophic lateral sclerosis in patients with hexanucleotide repeat expansions of C9ORF72. J Neurol Neurosurg Psychiatry 2013; 84: 79-87
236. Liu X, Milo M, Lawrence ND, Rattray M. Probe-level measurement error improves accuracy in detecting differential gene expression. Bioinformatics 2006; 22: 2107-2113
237. Tateishi T, Yamasaki R, Tanaka M, Matsushita T, Kikuchi H, Isobe N, Ohyagi Y, Kira J-I. CSF chemokine alterations related to the clinical course of amyotrophic lateral sclerosis. J Neuroimmunol 2010; 222: 76-81
238. Hautbergue GM, Hung M-L, Golovanov AP, Lian L-Y, Wilson SA. Mutually exclusive interactions drive handover of mRNA from export adaptors to TAP. Proc Natl Acad Sci USA 2008; 105: 5154-5159
239. Skourti-Stathaki K, Proudfoot NJ. A double-edged sword: R loops as threats to genome integrity and powerful regulators of gene expression. Genes Dev 2014; 28: 1384-1396
240. Dini Modigliani S, Morlando M, Errichelli L, Sabatelli M, Bozzoni I, An ALS. associated mutation in the FUS 3′-UTR disrupts a microRNA-FUS regulatory circuitry. Nat Commun 2014; 5: 4335
241. Heath PR, Kirby J, Shaw PJ. Investigating cell death mechanisms in amyotrophic lateral sclerosis using transcriptomics. Front Cell Neurosci 2013; 7: 259
242. Henriques A, De Aguilar J-LG. Can transcriptomics cut the gordian knot of amyotrophic lateral sclerosis? Curr Genomics 2011; 12: 506
243. Mitchell AC, Mirnics K. Gene expression profiling of the brain: pondering facts and fiction. Neurobiol Dis 2012; 45: 3-7
244. Domínguez-Sánchez MS, Sáez C, Japón MA, Aguilera A, Luna R. Differential expression of THOC1 and ALY mRNP biogenesis/export factors in human cancers. BMC Cancer 2011; 11: 77
245. Mori K, Arzberger T, Grässer FA, Gijselinck I, May S, Rentzsch K, Weng S-M, Schludi MH, van der Zee J, Cruts MR, Van Broeckhoven C, Kremmer E, Kretzschmar HA, Haass C, Edbauer D. Bidirectional transcripts of the expanded C9orf72 hexanucleotide repeat are translated into aggregating dipeptide repeat proteins. Acta Neuropathol 2013; 126: 881-893
246. Tanaka M, Chock PB, Stadtman ER. Oxidized messenger RNA induces translation errors. Proc Natl Acad Sci USA 2007; 104: 66-71
247. Singh M. Dysregulated A to I RNA editing and non-coding RNAs in neurodegeneration. Front Genet 2012; 3: 326
248. Shapiro E, Biezuner T, Linnarsson S. Single-cell sequencing-based technologies will revolutionize whole-organism science. Nature 2013; 14: 618-630
249. Martin I, Kim JW, Lee BD, Kang HC, Xu J-C, Jia H, Stankowski J, Kim M-S, Zhong J, Kumar M, Andrabi SA, Xiong Y, Dickson DW, Wszolek ZK, Pandey A, Dawson TM, Dawson VL. Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson's disease. Cell 2014; 157: 472-485