Neuroscience Bulletin

, Volume 30, Issue 4, pp 610–626 | Cite as

RNA binding proteins: a common denominator of neuronal function and dysfunction

Review

Abstract

In eukaryotic cells, gene activity is not directly reflected by protein levels because mRNA processing, transport, stability, and translation are co- and post-transcriptionally regulated. These processes, collectively known as the ribonome, are tightly controlled and carried out by a plethora of trans-acting RNA-binding proteins (RBPs) that bind to specific cis elements throughout the RNA sequence. Within the nervous system, the role of RBPs in brain function turns out to be essential due to the architectural complexity of neurons exemplified by a relatively small somal size and an extensive network of projections and connections. Thus far, RBPs have been shown to be indispensable for several aspects of neurogenesis, neurite outgrowth, synapse formation, and plasticity. Consequently, perturbation of their function is central in the etiology of an ever-growing spectrum of neurological diseases, including fragile X syndrome and the neurodegenerative disorders frontotemporal lobar degeneration and amyotrophic lateral sclerosis.

Keywords

alternative polyadenylation alternative splicing amyotrophic lateral sclerosis anti-Hu syndrome CPEB ELAV fragile X syndrome FMRP FUS HU HuB HuC HuD HuR neuron neurodegeneration Nova-1 Nova-2 paraneoplastic opsoclonus-myoclonus ataxia PTBP-2 PTBP-1 TDP-43 FTLD 

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References

  1. [1]
    Doxakis E. Principles of miRNA-target regulation in metazoan models. Int J Mol Sci 2013, 14: 16280–16302.PubMedCentralPubMedGoogle Scholar
  2. [2]
    Zheng S, Black DL. Alternative pre-mRNA splicing in neurons: growing up and extending its reach. Trends Genet 2013, 29: 442–448.PubMedGoogle Scholar
  3. [3]
    Elkon R, Ugalde AP, Agami R. Alternative cleavage and polyadenylation: extent, regulation and function. Nat Rev Genet 2013, 14: 496–506.PubMedGoogle Scholar
  4. [4]
    Mukherjee N, Corcoran DL, Nusbaum JD, Reid DW, Georgiev S, Hafner M, et al. Integrative regulatory mapping indicates that the RNA-binding protein HuR couples premRNA processing and mRNA stability. Mol Cell 2011, 43: 327–339.PubMedCentralPubMedGoogle Scholar
  5. [5]
    Polymenidou M, Lagier-Tourenne C, Hutt KR, Huelga SC, Moran J, Liang TY, et al. Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43. Nat Neurosci 2011, 14: 459–468.PubMedCentralPubMedGoogle Scholar
  6. [6]
    Jung MY, Lorenz L, Richter JD. Translational control by neuroguidin, a eukaryotic initiation factor 4E and CPEB binding protein. Mol Cell Biol 2006, 26: 4277–4287.PubMedCentralPubMedGoogle Scholar
  7. [7]
    Lim CS, Alkon DL. Protein kinase C stimulates HuD-mediated mRNA stability and protein expression of neurotrophic factors and enhances dendritic maturation of hippocampal neurons in culture. Hippocampus 2012, 22: 2303–2319.PubMedGoogle Scholar
  8. [8]
    Narayanan U, Nalavadi V, Nakamoto M, Thomas G, Ceman S, Bassell GJ, et al. S6K1 phosphorylates and regulates fragile X mental retardation protein (FMRP) with the neuronal protein synthesis-dependent mammalian target of rapamycin (mTOR) signaling cascade. J Biol Chem 2008, 283: 18478–18482.PubMedCentralPubMedGoogle Scholar
  9. [9]
    Lal A, Mazan-Mamczarz K, Kawai T, Yang X, Martindale JL, Gorospe M. Concurrent versus individual binding of HuR and AUF1 to common labile target mRNAs. EMBO J 2004, 23: 3092–3102.PubMedCentralPubMedGoogle Scholar
  10. [10]
    Ibrahim F, Nakaya T, Mourelatos Z. RNA dysregulation in diseases of motor neurons. Annu Rev Pathol 2012, 7: 323–352.PubMedGoogle Scholar
  11. [11]
    Wahl MC, Will CL, Luhrmann R. The spliceosome: design principles of a dynamic RNP machine. Cell 2009, 136: 701–718.PubMedGoogle Scholar
  12. [12]
    Jurica MS, Moore MJ. Pre-mRNA splicing: awash in a sea of proteins. Mol Cell 2003, 12: 5–14.PubMedGoogle Scholar
  13. [13]
    Pan Q, Shai O, Lee LJ, Frey BJ, Blencowe BJ. Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat Genet 2008, 40: 1413–1415.PubMedGoogle Scholar
  14. [14]
    Wang ET, Sandberg R, Luo S, Khrebtukova I, Zhang L, Mayr C, et al. Alternative isoform regulation in human tissue transcriptomes. Nature 2008, 456: 470–476.PubMedCentralPubMedGoogle Scholar
  15. [15]
    Kan Z, Rouchka EC, Gish WR, States DJ. Gene structure prediction and alternative splicing analysis using genomically aligned ESTs. Genome Res 2001, 11: 889–900.PubMedCentralPubMedGoogle Scholar
  16. [16]
    de la Grange P, Gratadou L, Delord M, Dutertre M, Auboeuf D. Splicing factor and exon profiling across human tissues. Nucleic Acids Res 2010, 38: 2825–2838.PubMedCentralPubMedGoogle Scholar
  17. [17]
    Castle JC, Zhang C, Shah JK, Kulkarni AV, Kalsotra A, Cooper TA, et al. Expression of 24,426 human alternative splicing events and predicted cis regulation in 48 tissues and cell lines. Nat Genet 2008, 40: 1416–1425.PubMedCentralPubMedGoogle Scholar
  18. [18]
    Clark TA, Schweitzer AC, Chen TX, Staples MK, Lu G, Wang H, et al. Discovery of tissue-specific exons using comprehensive human exon microarrays. Genome Biol 2007, 8: R64.PubMedCentralPubMedGoogle Scholar
  19. [19]
    Gray NK, Hentze MW. Regulation of protein synthesis by mRNA structure. Mol Biol Rep 1994, 19: 195–200.PubMedGoogle Scholar
  20. [20]
    Kozak M. Circ umstances and mechanisms of inhibition of translation by secondary structure in eucaryotic mRNAs. Mol Cell Biol 1989, 9: 5134–5142.PubMedCentralPubMedGoogle Scholar
  21. [21]
    Dyer JR, Michel S, Lee W, Castellucci VF, Wayne NL, Sossin WS. An activity-dependent switch to cap-independent translation triggered by eIF4E dephosphorylation. Nat Neurosci 2003, 6: 219–220.PubMedGoogle Scholar
  22. [22]
    Pinkstaff JK, Chappell SA, Mauro VP, Edelman GM, Krushel LA. Internal initiation of translation of five dendritically localized neuronal mRNAs. Proc Natl Acad Sci U S A 2001, 98: 2770–2775.PubMedCentralPubMedGoogle Scholar
  23. [23]
    Polydorides AD, Okano HJ, Yang YY, Stefani G, Darnell RB. A brain-enriched polypyrimidine tract-binding protein antagonizes the ability of Nova to regulate neuron-specific alternative splicing. Proc Natl Acad Sci U S A 2000, 97: 6350–6355.PubMedCentralPubMedGoogle Scholar
  24. [24]
    Romanelli MG, Lorenzi P, Morandi C. Organization of the human gene encoding heterogeneous nuclear ribonucleoprotein type I (hnRNP I) and characterization of hnRNP I related pseudogene. Gene 2000, 255: 267–272.PubMedGoogle Scholar
  25. [25]
    Romanelli MG, Lorenzi P, Morandi C. Identification and analysis of the human neural polypyrimidine tract binding protein (nPTB) gene promoter region. Gene 2005, 356: 11–18.PubMedGoogle Scholar
  26. [26]
    Boutz PL, Stoilov P, Li Q, Lin CH, Chawla G, Ostrow K, et al. A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons. Genes Dev 2007, 21: 1636–1652.PubMedCentralPubMedGoogle Scholar
  27. [27]
    Licatalosi DD, Yano M, Fak JJ, Mele A, Grabinski SE, Zhang C, et al. Ptbp2 represses adult-specific splicing to regulate the generation of neuronal precursors in the embryonic brain. Genes Dev 2012, 26: 1626–1642.PubMedCentralPubMedGoogle Scholar
  28. [28]
    Llorian M, Schwartz S, Clark TA, Hollander D, Tan LY, Spellman R, et al. Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB. Nat Struct Mol Biol 2010, 17: 1114–1123.PubMedCentralPubMedGoogle Scholar
  29. [29]
    Xue Y, Zhou Y, Wu T, Zhu T, Ji X, Kwon YS, et al. Genomewide analysis of PTB-RNA interactions reveals a strategy used by the general splicing repressor to modulate exon inclusion or skipping. Mol Cell 2009, 36: 996–1006.PubMedCentralPubMedGoogle Scholar
  30. [30]
    Makeyev EV, Zhang J, Carrasco MA, Maniatis T. The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol Cell 2007, 27: 435–448.PubMedCentralPubMedGoogle Scholar
  31. [31]
    Bronicki LM, Jasmin BJ. Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction. RNA 2013, 19: 1019–1037.PubMedGoogle Scholar
  32. [32]
    Deschenes-Furry J, Perrone-Bizzozero N, Jasmin BJ. The RNA-binding protein HuD: a regulator of neuronal differentiation, maintenance and plasticity. Bioessays 2006, 28: 822–833.PubMedGoogle Scholar
  33. [33]
    Hinman MN, Lou H. Diverse molecular functions of Hu proteins. Cell Mol Life Sci 2008, 65: 3168–3181.PubMedCentralPubMedGoogle Scholar
  34. [34]
    Pascale A, Amadio M, Quattrone A. Defining a neuron: neuronal ELAV proteins. Cell Mol Life Sci 2008, 65: 128–140.PubMedGoogle Scholar
  35. [35]
    Pascale A, Govoni S. The complex world of posttranscriptional mechanisms: is their deregulation a common link for diseases? Focus on ELAV-like RNA-binding proteins. Cell Mol Life Sci 2012, 69: 501–517.PubMedGoogle Scholar
  36. [36]
    Okano HJ, Darnell RB. A hierarchy of Hu RNA binding proteins in developing and adult neurons. J Neurosci 1997, 17: 3024–3037.PubMedGoogle Scholar
  37. [37]
    Good PJ. A conserved family of elav-like genes in vertebrates. Proc Natl Acad Sci U S A 1995, 92: 4557–4561.PubMedCentralPubMedGoogle Scholar
  38. [38]
    Akamatsu W, Fujihara H, Mitsuhashi T, Yano M, Shibata S, Hayakawa Y, et al. The RNA-binding protein HuD regulates neuronal cell identity and maturation. Proc Natl Acad Sci U S A 2005, 102: 4625–4630.PubMedCentralPubMedGoogle Scholar
  39. [39]
    Akamatsu W, Okano HJ, Osumi N, Inoue T, Nakamura S, Sakakibara S, et al. Mammalian ELAV-like neuronal RNA-binding proteins HuB and HuC promote neuronal development in both the central and the peripheral nervous systems. Proc Natl Acad Sci U S A 1999, 96: 9885–9890.PubMedCentralPubMedGoogle Scholar
  40. [40]
    Okano H, Kawahara H, Toriya M, Nakao K, Shibata S, Imai T. Function of RNA-binding protein Musashi-1 in stem cells. Exp Cell Res 2005, 306: 349–356.PubMedGoogle Scholar
  41. [41]
    Yano M, Okano HJ, Okano H. Involv ement of Hu and heterogeneous nuclear ribonucleoprotein K in neuronal differentiation through p21 mRNA post-transcriptional regulation. J Biol Chem 2005, 280: 12690–12699.PubMedGoogle Scholar
  42. [42]
    Ince-Dunn G, Okano HJ, Jensen KB, Park WY, Zhong R, Ule J, et al. Neuronal Elav-like (Hu) proteins regulate RNA splicing and abundance to control glutamate levels and neuronal excitability. Neuron 2012, 75: 1067–1080.PubMedCentralPubMedGoogle Scholar
  43. [43]
    Bolognani F, Merhege MA, Twiss J, Perrone-Bizzozero NI. Dendritic localization of the RNA-binding protein HuD in hippocampal neurons: association with polysomes and upregulation during contextual learning. Neurosci Lett 2004, 371: 152–157.PubMedGoogle Scholar
  44. [44]
    Pascale A, Gusev PA, Amadio M, Dottorini T, Govoni S, Alkon DL, et al. Increase of the RNA-binding protein HuD and posttranscriptional up-regulation of the GAP-43 gene during spatial memory. Proc Natl Acad Sci U S A 2004, 101: 1217–1222.PubMedCentralPubMedGoogle Scholar
  45. [45]
    Quattrone A, Pascale A, Nogues X, Zhao W, Gusev P, Pacini A, et al. Posttranscriptional regulation of gene expression in learning by the neuronal ELAV-like mRNA-stabilizing proteins. Proc Natl Acad Sci U S A 2001, 98: 11668–11673.PubMedCentralPubMedGoogle Scholar
  46. [46]
    Tiruchinapalli DM, Caron MG, Keene JD. Activity-dependent expression of ELAV/Hu RBPs and neuronal mRNAs in seizure and cocaine brain. J Neurochem 2008, 107: 1529–1543.PubMedGoogle Scholar
  47. [47]
    Tiruchinapalli DM, Ehlers MD, Keene JD. Activity-dependent expression of RNA binding protein HuD and its association with mRNAs in neurons. RNA Biol 2008, 5: 157–168.PubMedGoogle Scholar
  48. [48]
    Bolognani F, Qiu S, Tanner DC, Paik J, Perrone-Bizzozero NI, Weeber EJ. Associative and spatial learning and memory deficits in transgenic mice overexpressing the RNA-binding protein HuD. Neurobiol Learn Mem 2007, 87: 635–643.PubMedGoogle Scholar
  49. [49]
    Senties-Madrid H, Vega-Boada F. Paraneoplastic syndromes associated with anti-Hu antibodies. Isr Med Assoc J 2001, 3: 94–103.PubMedGoogle Scholar
  50. [50]
    Lebedeva S, Jens M, Theil K, Schwanhausser B, Selbach M, Landthaler M, et al. Transcriptome-wide analysis of regulatory interactions of the RNA-binding protein HuR. Mol Cell 2011, 43: 340–352.PubMedGoogle Scholar
  51. [51]
    Zhou HL, Hinman MN, Barron VA, Geng C, Zhou G, Luo G, et al. Hu proteins regulate alternative splicing by inducing localized histone hyperacetylation in an RNA-dependent manner. Proc Natl Acad Sci U S A 2011, 108: E627–635.PubMedCentralPubMedGoogle Scholar
  52. [52]
    Ratti A, Fallini C, Colombrita C, Pascale A, Laforenza U, Quattrone A, et al. Post-transcriptional regulation of neurooncological ventral antigen 1 by the neuronal RNA-binding proteins ELAV. J Biol Chem 2008, 283: 7531–7541.PubMedGoogle Scholar
  53. [53]
    Buckanovich RJ, Posner JB, Darnell RB. Nova, the paraneoplastic Ri antigen, is homologous to an RNA-binding protein and is specifically expressed in the developing motor system. Neuron 1993, 11: 657–672.PubMedGoogle Scholar
  54. [54]
    Hormigo A, Dalmau J, Rosenblum MK, River ME, Posner JB. Immunological and pathological study of anti-Ri-associated encephalopathy. Ann Neurol 1994, 36: 896–902.PubMedGoogle Scholar
  55. [55]
    Luque FA, Furneaux HM, Ferziger R, Rosenblum MK, Wray SH, Schold SC, Jr., et al. Anti-Ri: an antibody associated with paraneoplastic opsoclonus and breast cancer. Ann Neurol 1991, 29: 241–251.PubMedGoogle Scholar
  56. [56]
    Pranzatelli MR. The neurobiology of the opsoclon usmyoclonus syndrome. Clin Neuropharmacol 1992, 15: 186–228.PubMedGoogle Scholar
  57. [57]
    Racca C, Gardiol A, Eom T, Ule J, Triller A, Darnell RB. The Neuronal splicing factor nova co-localizes with target RNAs in the dendrite. Front Neural Circuits 2010, 4: 5.PubMedCentralPubMedGoogle Scholar
  58. [58]
    Yang YY, Yin GL, Darnell RB. The neuronal RNA-bin ding protein Nova-2 is implicated as the autoantigen targeted in POMA patients with dementia. Proc Natl Acad Sci U S A 1998, 95: 13254–13259.PubMedCentralPubMedGoogle Scholar
  59. [59]
    Jensen KB, Musunuru K, Lewis HA, Burley SK, Darnell RB. The tetranucleotide UCAY directs the specific recognition of RNA by the Nova K-homology 3 domain. Proc Natl Acad Sci U S A 2000, 97: 5740–5745.PubMedCentralPubMedGoogle Scholar
  60. [60]
    Jensen KB, Dredge BK, Stefani G, Zhong R, Buckanovich RJ, Okano HJ, et al. Nova-1 regulates neuron-specific alternative splicing and is essential for neuronal viability. Neuron 2000, 25: 359–371.PubMedGoogle Scholar
  61. [61]
    Yano M, Hayakawa-Yano Y, Mele A, Darnell RB. Nova2 regulates neuronal migration through an RNA switch in disabled-1 signaling. Neuron 2010, 66: 848–858.PubMedCentralPubMedGoogle Scholar
  62. [62]
    Ruggiu M, Herbst R, Kim N, Jevsek M, Fak JJ, Mann MA, et al. Rescuing Z+ agrin splicing in Nova null mice restores synapse formation and unmasks a physiologic defect in motor neuron firing. Proc Natl Acad Sci U S A 2009, 106: 3513–3518.PubMedCentralPubMedGoogle Scholar
  63. [63]
    Licatalosi DD, Mele A, Fak JJ, Ule J, Kayikci M, Chi SW, et al. HITS-CLIP yields genome-wide insights into brain alternative RNA processing. Nature 2008, 456: 464–469.PubMedCentralPubMedGoogle Scholar
  64. [64]
    Eom T, Zhang C, Wang H, Lay K, Fak J, Noebels JL, et al. NOVA-dependent regulation of cryptic NMD exons controls synaptic protein levels after seizure. Elife 2013, 2: e00178.PubMedCentralPubMedGoogle Scholar
  65. [65]
    Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 2006, 314: 130–133.PubMedGoogle Scholar
  66. [66]
    Ayala YM, Pantano S, D’Ambrogio A, Buratti E, Brindisi A, Marchetti C, et al. Human, Drosophila, and C.elegans TDP43: nucleic acid binding properties and splicing regulatory function. J Mol Biol 2005, 348: 575–588.PubMedGoogle Scholar
  67. [67]
    Buratti E, Baralle FE. Characterization and functional implications of the RNA binding properties of nuclear factor TDP-43, a novel splicing regulator of CFTR exon 9. J Biol Chem 2001, 276: 36337–36343.PubMedGoogle Scholar
  68. [68]
    Lattante S, Rouleau GA, Kabashi E. TARDBP and FUS mutation s associated with amyotrophic lateral sclerosis: summary and update. Hum Mutat 2013, 34: 812–826.PubMedGoogle Scholar
  69. [69]
    Fuentealba RA, Udan M, Bell S, Wegorzewska I, Shao J, Diamond MI, et al. Interaction with polyglutamine aggregates reveals a Q/N-rich domain in TDP-43. J Biol Chem 2010, 285: 26304–26314.PubMedCentralPubMedGoogle Scholar
  70. [70]
    Freibaum BD, Chitta RK, High AA, Taylor JP. Global analysis of TDP-43 interacting proteins reveals strong association with RNA splicing and translation machinery. J Proteome Res 2010, 9: 1104–1120.PubMedCentralPubMedGoogle Scholar
  71. [71]
    Tollervey JR, Curk T, Rogelj B, Briese M, Cereda M, Kayikci M, et al. Characterizing the RNA targets and position-dependent splicing regulation by TDP-43. Nat Neurosci 2011, 14: 452–458.PubMedCentralPubMedGoogle Scholar
  72. [72]
    Fiesel FC, Voigt A, Weber SS, Van den Haute C, Waldenmaier A, Gorner K, et al. Knockdown of transactive response DNA-binding protein (TDP-43) downregulates histone deacetylase 6. EMBO J 2010, 29: 209–221.PubMedCentralPubMedGoogle Scholar
  73. [73]
    Volkening K, Leystra-Lantz C, Yang W, Jaffee H, Strong MJ. Tar DNA binding protein of 43 kDa (TDP-43), 14-3-3 proteins and copper/zinc superoxide dismutase (SOD1) interact to modulate NFL mRNA stability. Implications for altered RNA processing in amyotrophic lateral sclerosis (ALS). Brain Res 2009, 1305: 168–182.PubMedGoogle Scholar
  74. [74]
    Wang IF, Wu LS, Chang HY, Shen CK. TDP-43, the signature protein of FTLD-U, is a neuronal activity-responsive factor. J Neurochem 2008, 105: 797–806.PubMedGoogle Scholar
  75. [75]
    Feiguin F, Godena VK, Romano G, D’Ambrogio A, Klima R, Baralle FE. Depletion of TDP-43 affects Drosophila motoneurons terminal synapsis and locomotive behavior. FEBS Lett 2009, 583: 1586–1592.PubMedGoogle Scholar
  76. [76]
    Sephton CF, Good SK, Atkin S, Dewey CM, Mayer P, 3rd, Herz J, et al. TDP-43 is a developmentally regulated protein essential for early embryonic development. J Biol Chem 2010, 285: 6826–6834.PubMedCentralPubMedGoogle Scholar
  77. [77]
    Iko Y, Kodama TS, Kasai N, Oyama T, Morita EH, Muto T, et al. Domai n architectures and characterization of an RNAbinding protein, TLS. J Biol Chem 2004, 279: 44834–44840.PubMedGoogle Scholar
  78. [78]
    Lerga A, Hallier M, Delva L, Orvain C, Gallais I, Marie J, et al. Identification of an RNA binding specificity for the potential splicing factor TLS. J Biol Chem 2001, 276: 6807–6816.PubMedGoogle Scholar
  79. [79]
    Dormann D, Rodde R, Edbauer D, Bentmann E, Fischer I, Hruscha A, et al. ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import. EMBO J 2010, 29: 2841–2857.PubMedCentralPubMedGoogle Scholar
  80. [80]
    Kato M, Han TW, Xie S, Shi K, Du X, Wu LC, et al. Cellfree formation of RNA granules: low complexity sequence domains form dynamic fibers within hydrogels. Cell 2012, 149: 753–767.PubMedGoogle Scholar
  81. [81]
    Kwiatkowski TJ, Jr., Bosco DA, Leclerc AL, Tamrazian E, Vanderburg CR, Russ C, et al. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 2009, 323: 1205–1208.PubMedGoogle Scholar
  82. [82]
    Vance C, Rogelj B, Hortobagyi T, De Vos KJ, Nishimura AL, Sreedharan J, et al. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 2009, 323: 1208–1211.PubMedGoogle Scholar
  83. [83]
    Gerbino V, Carri MT, Cozzolino M, Achsel T. Mislocalised FUS mutants stal l spliceosomal snRNPs in the cytoplasm. Neurobiol Dis 2013, 55: 120–128.PubMedGoogle Scholar
  84. [84]
    Meissner M, Lopato S, Gotzmann J, Sauermann G, Barta A. Proto-oncoprotein TLS/FUS is associated to the nuclear matrix and complexed with splicing factors PTB, SRm160, and SR proteins. Exp Cell Res 2003, 283: 184–195.PubMedGoogle Scholar
  85. [85]
    Schwartz JC, Ebmeier CC, Podell ER, Heimiller J, Taatjes DJ, Cech TR. FUS b inds the CTD of RNA polymerase II and regulates its phosphorylation at Ser2. Genes Dev 2012, 26: 2690–2695.PubMedCentralPubMedGoogle Scholar
  86. [86]
    Braunschweig U, Gueroussov S, Plocik AM, Graveley BR, Blencowe BJ. Dynamic i ntegration of splicing within gene regulatory pathways. Cell 2013, 152: 1252–1269.PubMedCentralPubMedGoogle Scholar
  87. [87]
    Lagier-Tourenne C, Polymenidou M, Hutt KR, Vu AQ, Baughn M, Huelga SC, et al. Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long premRNAs. Nat Neurosci 2012, 15: 1488–1497.PubMedCentralPubMedGoogle Scholar
  88. [88]
    Ishigaki S, Masuda A, Fujioka Y, Iguchi Y, Katsuno M, Shibata A, et al. Positi on-dependent FUS-RNA interactions regulate alternative splicing events and transcriptions. Sci Rep 2012, 2: 529.PubMedCentralPubMedGoogle Scholar
  89. [89]
    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.PubMedCentralPubMedGoogle Scholar
  90. [90]
    Rogelj B, Easton LE, Bogu GK, Stanton LW, Rot G, Curk T, et al. Widespread binding of FUS along nascent RNA regulates alternative splicing in the brain. Sci Rep 2012, 2:603.PubMedCentralPubMedGoogle Scholar
  91. [91]
    Hicks GG, Singh N, Nashabi A, Mai S, Bozek G, Klewes L, et al. Fus deficiency in mice results in defective B-lymphocyte development and activation, high levels of chromosomal instability and perinatal death. Nat Genet 2000, 24: 175–179.PubMedGoogle Scholar
  92. [92]
    Fujii R, Okabe S, Urushido T, Inoue K, Yoshimura A, Tachibana T, et al. The RNA binding protein TLS is translocated to dendritic spines by mGluR5 activation and regulates spine morphology. Curr Biol 2005, 15: 587–593.PubMedGoogle Scholar
  93. [93]
    Mitchell JC, McGoldrick P, Vance C, Hortobagyi T, Sreedharan J, Rogelj B, et al. Overexpression of human wildtype FUS causes progressive motor neuron degeneration in an age- and dose-dependent fashion. Acta Neuropathol 2013, 125: 273–288.PubMedCentralPubMedGoogle Scholar
  94. [94]
    Sudhof TC. Neuroligins and neurexins link synaptic function to cognitive disease. Nature 2008, 455: 903–911.PubMedCentralPubMedGoogle Scholar
  95. [95]
    Hirokawa N, Niwa S, Tanaka Y. Molecular motors in neurons: transport mechanisms and roles in brain function, development, and disease. Neuron 2010, 68: 610–638.PubMedGoogle Scholar
  96. [96]
    Santos MS LH, Voglmaier SM. Synaptic vesicle protein trafficking at the glutamate sy napse. Neuroscience 2009, 158: 189–203.PubMedCentralPubMedGoogle Scholar
  97. [97]
    Christie SB, Akins MR, Schwob JE, Fallon JR. The FXG: a presynaptic fragile X granule expressed in a subset of developing brain circuits. J Neurosci 2009, 29: 1514–1524.PubMedCentralPubMedGoogle Scholar
  98. [98]
    Hinds HL, Ashley CT, Sutcliffe JS, Nelson DL, Warren ST, Housman DE, et al. Tissue spe cific expression of FMR-1 provides evidence for a functional role in fragile X syndrome. Nat Genet 1993, 3: 36–43.PubMedGoogle Scholar
  99. [99]
    Pieretti M, Zhang FP, Fu YH, Warren ST, Oostra BA, Caskey CT, et al. Absence of express ion of the FMR-1 gene in fragile X syndrome. Cell 1991, 66: 817–822.PubMedGoogle Scholar
  100. [100]
    Verkerk AJ, Pieretti M, Sutcliffe JS, Fu YH, Kuhl DP, Pizzuti A, et al. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 1991, 65: 905–914.PubMedGoogle Scholar
  101. [101]
    Antar LN, Li C, Zhang H, Carroll RC, Bassell GJ. Local functions for FMRP in axon growth cone motility and activitydependent regulation of filopodia and spine synapses. Mol Cell Neurosci 2006, 32: 37–48.PubMedGoogle Scholar
  102. [102]
    Ashley CT, Jr., Wilkinson KD, Reines D, Warren ST. FMR1 protein: conserved RNP family domains and selective RNA binding. Science 1993, 262: 563–566.PubMedGoogle Scholar
  103. [103]
    Darnell JC, Van Driesche SJ, Zhang C, Hung KY, Mele A, Fraser CE, et al. FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell 2011, 146: 247–261.PubMedCentralPubMedGoogle Scholar
  104. [104]
    Feng Y, Gutekunst CA, Eberhart DE, Yi H, Warren ST, Hersch SM. Fragile X mental retardation protein: nucleocytoplasmic shuttling and association with somatodendritic ribosomes. J Neurosci 1997, 17: 1539–1547.PubMedGoogle Scholar
  105. [105]
    Khandjian EW, Huot ME, Tremblay S, Davidovic L, Mazroui R, Bardoni B. Biochemical evidence f or the association of fragile X mental retardation protein with brain polyribosomal ribonucleoparticles. Proc Natl Acad Sci U S A 2004, 101: 13357–13362.PubMedCentralPubMedGoogle Scholar
  106. [106]
    Stefani G, Fraser CE, Darnell JC, Darnell RB. Fragile X mental retardation protein is associa ted with translating polyribosomes in neuronal cells. J Neurosci 2004, 24: 7272–7276.PubMedGoogle Scholar
  107. [107]
    Ramos A, Hollingworth D, Pastore A. G-quartet-dependent recognition between the FMRP RGG box and RNA. RNA 2003, 9: 1198–1207.PubMedCentralPubMedGoogle Scholar
  108. [108]
    Siomi H, Siomi MC, Nussbaum RL, Dreyfuss G. The protein product of the fragile X gene, FMR1, ha s characteristics of an RNA-binding protein. Cell 1993, 74: 291–298.PubMedGoogle Scholar
  109. [109]
    De Boulle K, Verkerk AJ, Reyniers E, Vits L, Hendrickx J, Van Roy B, et al. A point mutation in the FMR-1 gene associated with fragile X mental retardation. Nat Genet 1993, 3: 31–35.PubMedGoogle Scholar
  110. [110]
    Zang JB, Nosyreva ED, Spencer CM, Volk LJ, Musunuru K, Zhong R, et al. A mouse model of the human Fragile X syndrome I304N mutation. PLoS Genet 2009, 5: e1000758.PubMedCentralPubMedGoogle Scholar
  111. [111]
    Darnell JC, Fraser CE, Mostovetsky O, Stefani G, Jones TA, Eddy SR, et al. Kissing complex RNAs m ediate interaction between the Fragile-X mental retardation protein KH2 domain and brain polyribosomes. Genes Dev 2005, 19: 903–918.PubMedCentralPubMedGoogle Scholar
  112. [112]
    Mazroui R, Huot ME, Tremblay S, Filion C, Labelle Y, Khandjian EW. Trapping of messenger RNA by Fr agile X Mental Retardation protein into cytoplasmic granules induces translation repression. Hum Mol Genet 2002, 11: 3007–3017.PubMedGoogle Scholar
  113. [113]
    Muddashetty RS, Nalavadi VC, Gross C, Yao X, Xing L, Laur O, et al. Reversible inhibition of PSD-95 mRNA translation by miR-125a, FMRP phosphorylation, and mGluR signaling. Mol Cell 2011, 42: 673–688.PubMedCentralPubMedGoogle Scholar
  114. [114]
    Dictenberg JB, Swanger SA, Antar LN, Singer RH, Bassell GJ. A direct role for FMRP in activity-depen dent dendritic mRNA transport links filopodial-spine morphogenesis to fragile X syndrome. Dev Cell 2008, 14: 926–939.PubMedCentralPubMedGoogle Scholar
  115. [115]
    Theis M, Si K, Kandel ER. Two previously undescribed members of the mouse CPEB family of genes and th eir inducible expression in the principal cell layers of the hippocampus. Proc Natl Acad Sci U S A 2003, 100: 9602–9607.PubMedCentralPubMedGoogle Scholar
  116. [116]
    Wu L, Wells D, Tay J, Mendis D, Abbott MA, Barnitt A, et al. CPEB-mediated cytoplasmic polyadenylation and the regulation of experience-dependent translation of alpha-CaMKII mRNA at synapses. Neuron 1998, 21: 1129–1139.PubMedGoogle Scholar
  117. [117]
    Huang YS, Kan MC, Lin CL, Richter JD. CPEB3 and CPEB4 in neurons: analysis of RNA-binding specificity a nd translational control of AMPA receptor GluR2 mRNA. EMBO J 2006, 25: 4865–4876.PubMedCentralPubMedGoogle Scholar
  118. [118]
    Hake LE, Mendez R, Richter JD. Specificity of RNA binding by CPEB: requirement for RNA recognition motif s and a novel zinc finger. Mol Cell Biol 1998, 18: 685–693.PubMedCentralPubMedGoogle Scholar
  119. [119]
    Richter JD. CPEB: a life in translation. Trends Biochem Sci 2007, 32: 279–285.PubMedGoogle Scholar
  120. [120]
    Udagawa T, Swanger S A, Takeuchi K, Kim JH, Nalavadi V, Shin J, et al. Bidirectional control of mRNA trans lation and synaptic plasticity by the cytoplasmic polyadenylation complex. Mol Cell 2012, 47: 253–266.PubMedCentralPubMedGoogle Scholar
  121. [121]
    Barnard DC, Ryan K, Manley JL, Richter JD. Symplekin and xGLD-2 are required for CPEB-mediated cytoplasmic polyadenylation. Cell 2004, 119: 641–651.PubMedGoogle Scholar
  122. [122]
    Kim JH, Richter JD. RINGO/cdk1 and CPEB mediate poly(A) tail stabilization and translational regulation by ePAB. Genes Dev 2007, 21: 2571–2579.PubMedCentralPubMedGoogle Scholar
  123. [123]
    Atkins CM, Davare MA, Oh MC, Derkach V, Soderling TR. Bidirectional regulation of cytoplasmic polyadenylati on element-binding protein phosphorylation by Ca2+/calmodulindependent protein kinase II and protein phosphatase 1 during hippocampal long-term potentiation. J Neurosci 2005, 25: 5604–5610.PubMedGoogle Scholar
  124. [124]
    Atkins CM, Nozaki N, Shigeri Y, Soderling TR. Cytoplasmic polyadenylation element binding protein-dependent protein synthesis is regulated by calcium/calmodulin-dependent protein kinase II. J Neurosci 2004, 24: 5193–5201.PubMedGoogle Scholar
  125. [125]
    Huang YS, Jung MY, Sarkissian M, Richter JD. N-methyl-D-aspartate receptor signaling results in Aurora kinase — catalyzed CPEB phosphorylation and alpha CaMKII mRNA polyadenylation at synapses. EMBO J 2002, 21: 2139–2148.PubMedCentralPubMedGoogle Scholar
  126. [126]
    Alarcon JM, Hodgman R, Theis M, Huang YS, Kandel ER, Richter JD. Selective modulation of some forms of schaffe r collateral-CA1 synaptic plasticity in mice with a disruption of the CPEB-1 gene. Learn Mem 2004, 11: 318–327.PubMedCentralPubMedGoogle Scholar
  127. [127]
    Berger-Sweeney J, Zearfoss NR, Richter JD. Reduced extinction of hippocampal-dependent memories in CPEB knockou t mice. Learn Mem 2006, 13: 4–7.PubMedGoogle Scholar
  128. [128]
    Zearfoss NR, Alarcon JM, Trifilieff P, Kandel E, Richter JD. A molecular circuit composed of CPEB-1 and c-Jun co ntrols growth hormone-mediated synaptic plasticity in the mouse hippocampus. J Neurosci 2008, 28: 8502–8509.PubMedCentralPubMedGoogle Scholar
  129. [129]
    McEvoy M, Cao G, Montero Llopis P, Kundel M, Jones K, Hofler C, et al. Cytoplasmic polyadenylation element bindin g protein 1-mediated mRNA translation in Purkinje neurons is required for cerebellar long-term depression and motor coordination. J Neurosci 2007, 27: 6400–6411.PubMedGoogle Scholar
  130. [130]
    Legendre M, Ritchie W, Lopez F, Gautheret D. Differential repression of alternative transcripts: a screen for miRN A targets. PLoS Comput Biol 2006, 2: e43.PubMedCentralPubMedGoogle Scholar
  131. [131]
    Chi SW, Hannon GJ, Darnell RB. An alternative mode of microRNA target recognition. Nat Struct Mol Biol 2012, 19:321–327.PubMedCentralPubMedGoogle Scholar
  132. [132]
    Ji Z, Lee JY, Pan Z, Jiang B, Tian B. Progressive lengthening of 3’ untranslated regions of mRNAs by alternative po lyadenylation during mouse embryonic development. Proc Natl Acad Sci U S A 2009, 106: 7028–7033.PubMedCentralPubMedGoogle Scholar
  133. [133]
    Sandberg R, Neilson JR, Sarma A, Sharp PA, Burge CB. Proliferating cells express mRNAs with shortened 3’ untranslate d regions and fewer microRNA target sites. Science 2008, 320: 1643–1647.PubMedCentralPubMedGoogle Scholar
  134. [134]
    Paschou M, Paraskevopoulou MD, Vlachos IS, Koukouraki P, Hatzigeorgiou AG, Doxakis E. miRNA Regulons Associated with Synaptic Function. PLoS One 2012, 7: e46189.PubMedCentralPubMedGoogle Scholar
  135. [135]
    An JJ, Gharami K, Liao GY, Woo NH, Lau AG, Vanevski F, et al. Distinct role of long 3’ UTR BDNF mRNA in spine morphol ogy and synaptic plasticity in hippocampal neurons. Cell 2008, 134: 175–187.PubMedCentralPubMedGoogle Scholar
  136. [136]
    Liao GY, An JJ, Gharami K, Waterhouse EG, Vanevski F, Jones KR, et al. Dendritically targeted Bdnf mRNA is essential f or energy balance and response to leptin. Nat Med 2012, 18: 564–571.PubMedCentralPubMedGoogle Scholar
  137. [137]
    Lau AG, Irier HA, Gu J, Tian D, Ku L, Liu G, et al. Distinct 3’UTRs differentially regulate activity-dependent translat ion of brain-derived neurotrophic factor (BDNF). Proc Natl Acad Sci U S A 2010, 107: 15945–15950.PubMedCentralPubMedGoogle Scholar
  138. [138]
    Oe S, Yoneda Y. Cytoplasmic polyadenylation element-like sequences are involved in dendritic targeting of BDNF mRNA in h ippocampal neurons. FEBS Lett 2010, 584: 3424–3430.PubMedGoogle Scholar
  139. [139]
    Allen M, Bird C, Feng W, Liu G, Li W, Perrone-Bizzozero NI, et al. HuD promotes BDNF expression in brain neurons via sele ctive stabilization of the BDNF long 3’UTR mRNA. PLoS One 2013, 8: e55718.PubMedCentralPubMedGoogle Scholar
  140. [140]
    Tian B, Hu J, Zhang H, Lutz CS. A large-scale analysis of mRNA polyadenylation of human and mouse genes. Nucleic Acids Re s 2005, 33: 201–212.Google Scholar
  141. [141]
    Beaudoing E, Freier S, Wyatt JR, Claverie JM, Gautheret D. Patterns of variant polyadenylation signal usage in human genes. Genome Res 2000, 10: 1001–1010.PubMedCentralPubMedGoogle Scholar
  142. [142]
    Ji Z, Tian B. Reprogramming of 3’ untranslated regions of mRNAs by alternative polyadenylation in generation of pluripotent stem cells from different cell types. PLoS One 2009, 4: e8419.PubMedCentralPubMedGoogle Scholar
  143. [143]
    Nunes NM, Li W, Tian B, Furger A. A functional human Poly(A) site requires only a potent DSE and an A-rich upstream sequenc e. EMBO J 2010, 29: 1523–1536.PubMedCentralPubMedGoogle Scholar
  144. [144]
    Zhu H, Zhou HL, Hasman RA, Lou H. Hu proteins regulate polyadenylation by blocking sites containing U-rich sequences. J Biol Chem 2007, 282: 2203–2210.PubMedGoogle Scholar
  145. [145]
    Hilgers V, Lemke SB, Levine M. ELAV mediates 3’ UTR extension in the Drosophila nervous system. Genes Dev 2012, 26: 2259–2264.PubMedCentralPubMedGoogle Scholar
  146. [146]
    Al-Ahmadi W, Al-Ghamdi M, Al-Haj L, Al-Saif M, Khabar KS. Alternative polyadenylation variants of the RNA binding protein, HuR: abundance, role of AU-rich elements and auto-Regulation. Nucleic Acids Res 2009, 37: 3612–3624.PubMedCentralPubMedGoogle Scholar
  147. [147]
    Dai W, Zhang G, Makeyev EV. RNA-binding protein HuR autoregulates its expression by promoting alternative polyadenylation site usage. Nucleic Acids Res 2012, 40: 787–800.PubMedCentralPubMedGoogle Scholar
  148. [148]
    Mansfield KD, Keene JD. Neuron-specific ELAV/Hu proteins suppress HuR mRNA during neuronal differentiation by alternative polyad enylation. Nucleic Acids Res 2012, 40: 2734–2746.PubMedCentralPubMedGoogle Scholar
  149. [149]
    Jacobsen A, Wen J, Marks DS, Krogh A. Signatures of RNA binding proteins globally coupled to effective microRNA target sites. Gen ome Res 2010, 20: 1010–1019.Google Scholar
  150. [150]
    Larsson E, Sander C, Marks D. mRNA turnover rate limits siRNA and microRNA efficacy. Mol Syst Biol 2010, 6: 433.PubMedCentralPubMedGoogle Scholar
  151. [151]
    Srikantan S, Tominaga K, Gorospe M. Functional interplay between RNA-binding protein HuR and microRNAs. Curr Protein Pept Sci 2012, 13: 372–379.PubMedCentralPubMedGoogle Scholar
  152. [152]
    Abdelmohsen K, Srikantan S, Kuwano Y, Gorospe M. miR-519 reduces cell proliferation by lowering RNA-binding protein HuR levels. Pro c Natl Acad Sci U S A 2008, 105: 20297–20302.Google Scholar
  153. [153]
    Guo X, Wu Y, Hartley RS. MicroRNA-125a represses cell growth by targeting HuR in breast cancer. RNA Biol 2009, 6: 575–583.PubMedCentralPubMedGoogle Scholar
  154. [154]
    Young LE, Moore AE, Sokol L, Meisner-Kober N, Dixon DA. The mRNA stability factor HuR inhibits microRNA-16 targeting of COX-2. Mol Ca ncer Res 2012, 10: 167–180.Google Scholar
  155. [155]
    Castelo-Branco P, Furger A, Wollerton M, Smith C, Moreira A, Proudfoot N. Polypyrimidine tract binding protein modulates efficiency of polyadenylation. Mol Cell Biol 2004, 24: 4174–4183.PubMedCentralPubMedGoogle Scholar
  156. [156]
    Millevoi S, Decorsiere A, Loulergue C, Iacovoni J, Bernat S, Antoniou M, et al. A physical and functional link between splicing factors promotes pre-mRNA 3’ end processing. Nucleic Acids Res 2009, 37: 4672–4683.PubMedCentralPubMedGoogle Scholar
  157. [157]
    Dobson CM. Protein folding and misfolding. Nature 2003, 426: 884–890.PubMedGoogle Scholar
  158. [158]
    Dobson CM. Protein misfolding, evolution and disease. Trends Biochem Sci 1999, 24: 329–332.PubMedGoogle Scholar
  159. [159]
    Daigle JG, Lanson NA, Jr., Smith RB, Casci I, Maltare A, Monaghan J, et al. RNA-binding ability of FUS regulates neurodegeneration, cytopl asmic mislocalization and incorporation into stress granules associated with FUS carrying ALS-linked mutations. Hum Mol Genet 2013, 22: 1193–1205.PubMedCentralPubMedGoogle Scholar
  160. [160]
    Johnson BS, Snead D, Lee JJ, McCaffery JM, Shorter J, Gitler AD. TDP-43 is intrinsically aggregation-prone, and amyotrophic lateral scleros is-linked mutations accelerate aggregation and increase toxicity. J Biol Chem 2009, 284: 20329–20339.PubMedCentralPubMedGoogle Scholar
  161. [161]
    Sun Z, Diaz Z, Fang X, Hart MP, Chesi A, Shorter J, et al. Molecular determinants and genetic modifiers of aggregation and toxicity for the ALS disease protein FUS/TLS. PLoS Biol 2011, 9: e1000614.PubMedCentralPubMedGoogle Scholar
  162. [162]
    Voigt A, Herholz D, Fiesel FC, Kaur K, Muller D, Karsten P, et al. TDP-43-mediated neuron loss in vivo requires RNA-binding activity. PLoS One 2010, 5: e12247.PubMedCentralPubMedGoogle Scholar
  163. [163]
    DeJesus-Hernandez M, Mackenzie IR, Boeve BF, Boxer AL, Baker M, Rutherford NJ, et al. Expanded GGGGCC hexanucleotide repeat in noncoding reg ion of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 2011, 72: 245–256.PubMedCentralPubMedGoogle Scholar
  164. [164]
    Hagerman PJ, Hagerman RJ. The fragile-X premutation: a maturing perspective. Am J Hum Genet 2004, 74: 805–816.PubMedCentralPubMedGoogle Scholar
  165. [165]
    Renton AE, Majounie E, Waite A, Simon-Sanchez J, Rollinson S, Gibbs JR, et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of ch romosome 9p21-linked ALS-FTD. Neuron 2011, 72: 257–268.PubMedCentralPubMedGoogle Scholar
  166. [166]
    Shelkovnikova TA, Robinson HK, Troakes C, Ninkina N, Buchman VL. Compromised paraspeckle formation as a pathogenic factor in FUSopathies. Hum M ol Genet 2014.Google Scholar
  167. [167]
    Gilks N, Kedersha N, Ayodele M, Shen L, Stoecklin G, Dember LM, et al. Stress granule assembly is mediated by prion-like aggregation of TIA-1. Mol Biol Cell 2004, 15: 5383–5398.PubMedCentralPubMedGoogle Scholar
  168. [168]
    Kiebler MA, Bassell GJ. Neuronal RNA granules: movers and makers. Neuron 2006, 51: 685–690.PubMedGoogle Scholar
  169. [169]
    Wang DO, Martin KC, Zukin RS. Spatially restri cting gene expression by local translation at synapses. Trends Neurosci 2010, 33: 173–182.PubMedCentralPubMedGoogle Scholar
  170. [170]
    Bosco DA, Lemay N, Ko HK, Zhou H, Burke C, Kwiatkowski TJ, Jr., et al. Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate in to stress granules. Hum Mol Genet 2010, 19: 4160–4175.PubMedCentralPubMedGoogle Scholar
  171. [171]
    Colombrita C, Zennaro E, Fallini C, Weber M, Sommacal A, Buratti E, et al. TDP-43 is recruited to stress granules in conditions of oxidative insult. J Neurochem 2009, 111: 1051–1061.PubMedGoogle Scholar
  172. [172]
    Elden AC, Kim HJ, Hart MP, Chen-Plotkin AS, Johnson BS, Fang X, et al. Ataxin-2 intermediate-length polyglutamine expansions are associated with inc reased risk for ALS. Nature 2010, 466: 1069–1075.PubMedCentralPubMedGoogle Scholar
  173. [173]
    Hart MP, Gitler AD. ALS-associated ataxin 2 polyQ expansions enhance stress-induced caspase 3 activation and increase TDP-43 pathological modificatio ns. J Neurosci 2012, 32: 9133–9142.PubMedCentralPubMedGoogle Scholar
  174. [174]
    Hua Y, Zhou J. Survival motor neuron protein facilitates assembly of stress granules. FEBS Lett 2004, 572: 69–74.PubMedGoogle Scholar
  175. [175]
    Liu-Yesucevitz L, Bilgutay A, Zhang YJ, Vanderweyde T, Citro A, Mehta T, et al. Tar DNA binding protein-43 (TDP-43) associates with stress granules: an alysis of cultured cells and pathological brain tissue. PLoS One 2010, 5: e13250.PubMedCentralPubMedGoogle Scholar
  176. [176]
    King A, Sweeney F, Bodi I, Troakes C, Maekawa S, Al-Sarraj S. Abnormal TDP-43 expression is identified in the neocortex in cases of dementia pugilistic a, but is mainly confined to the limbic system when identified in high and moderate stages of Alzheimer’s disease. Neuropathology 2010, 30: 408–419.PubMedGoogle Scholar
  177. [177]
    McKee AC, Gavett BE, Stern RA, Nowinski CJ, Cantu RC, Kowall NW, et al. TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopath y. J Neuropathol Exp Neurol 2010, 69: 918–929.PubMedCentralPubMedGoogle Scholar
  178. [178]
    Vanderweyde T, Yu H, Varnum M, Liu-Yesucevitz L, Citro A, Ikezu T, et al. Contrasting pathology of the stress granule proteins TIA-1 and G3BP in tauopath ies. J Neurosci 2012, 32: 8270–8283.PubMedCentralPubMedGoogle Scholar
  179. [179]
    Buchan JR, Kolaitis RM, Taylor JP, Parker R. Eukaryotic stress granules are cleared by autophagy and Cdc48/VCP function. Cell 2013, 153: 1461–1474.PubMedCentralPubMedGoogle Scholar
  180. [180]
    Cuervo AM, Dice JF. Age-related decline in chaperonemediated autophagy. J Biol Chem 2000, 275: 31505–31513.PubMedGoogle Scholar
  181. [181]
    Wolozin B. Regulated protein aggregation: stress granules and neurodegeneration. Mol Neurodegener 2012, 7: 56.PubMedCentralPubMedGoogle Scholar
  182. [182]
    Cougot N, Bhattacharyya SN, Tapia-Arancibia L, Bordonne R, Filipowicz W, Bertrand E, et al. Dendrites of mammalian neurons contain specialized P-body-like s tructures that respond to neuronal activation. J Neurosci 2008, 28: 13793–13804.PubMedGoogle Scholar
  183. [183]
    Vessey JP, Vaccani A, Xie Y, Dahm R, Karra D, Kiebler MA, et al. Dendritic localization of the translational repressor Pumilio 2 and its contribution to dend ritic stress granules. J Neurosci 2006, 26: 6496–6508.PubMedGoogle Scholar
  184. [184]
    Mallucci GR. Prion neurodegeneration: starts and stops at the synapse. Prion 2009, 3: 195–201.PubMedCentralPubMedGoogle Scholar
  185. [185]
    Selkoe DJ. Alzheimer’s disease is a synaptic failure. Sci ence 2002, 298: 789–791.Google Scholar
  186. [186]
    Shahidullah M, Le Marchand SJ, Fei H, Zhang J, Pandey UB, Dalva MB, et al. Defects in synapse structure and function precede motor neuron degeneration in drosop hila models of FUS-Related ALS. J Neurosci 2013, 33: 19590–19598.PubMedCentralPubMedGoogle Scholar

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© Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Laboratory of Molecular and Cellular Neuroscience, Center of Basic NeuroscienceBiomedical Research Foundation of the Academy of AthensAthensGreece

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