Prion-like domains as epigenetic regulators, scaffolds for subcellular organization, and drivers of neurodegenerative disease

Brain Research

Volumn 1647, Issue , 2016, Pages 9-18

  March, Zachary M ^a   King, Oliver D ^b   Shorter, James ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

Author keywords

ALS; Disaggregase; Phase transition; Prion; Prion like domains; RNA binding proteins

Indexed keywords

AMINO ACID; ATAXIN 1; ATAXIN 2; EWSR1 PROTEIN; HNRNPA1 PROTEIN; HNRNPA2 PROTEIN; NUCLEIC ACID BINDING PROTEIN; PRION PROTEIN; PROTEIN AGGREGATE; TAF15 PROTEIN; TAR DNA BINDING PROTEIN; UNCLASSIFIED DRUG; ATXN1 PROTEIN, HUMAN; ATXN2 PROTEIN, HUMAN; CALMODULIN BINDING PROTEIN; DNA BINDING PROTEIN; EWSR1 PROTEIN, HUMAN; FUS PROTEIN, HUMAN; HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN GROUP A B; HNRNP A1; HNRNP A2; RNA BINDING PROTEIN; RNA BINDING PROTEIN FUS; TAF15 PROTEIN, HUMAN; TATA BINDING PROTEIN ASSOCIATED FACTOR; TDP-43 PROTEIN, HUMAN;

AMINO ACID COMPOSITION; DEGENERATIVE DISEASE; ENVIRONMENTAL STRESS; EPIGENETICS; HUMAN; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN MISFOLDING; PROTEIN STRUCTURE; REVIEW; YEAST; ANIMAL; CELL ORGANELLE; GENETIC EPIGENESIS; GENETICS; METABOLISM; PROTEIN DOMAIN; SACCHAROMYCES CEREVISIAE;

ANIMALS; ATAXIN-1; ATAXIN-2; CALMODULIN-BINDING PROTEINS; DNA-BINDING PROTEINS; EPIGENESIS, GENETIC; HETEROGENEOUS-NUCLEAR RIBONUCLEOPROTEIN GROUP A-B; HUMANS; NEURODEGENERATIVE DISEASES; ORGANELLES; PRION PROTEINS; PROTEIN DOMAINS; RNA-BINDING PROTEIN FUS; RNA-BINDING PROTEINS; SACCHAROMYCES CEREVISIAE; TATA-BINDING PROTEIN ASSOCIATED FACTORS;

EID: 84962106306     PISSN: 00068993     EISSN: 18726240     Source Type: Journal    
DOI: 10.1016/j.brainres.2016.02.037     Document Type: Review

References (182)

1. Aguzzi, A., Lakkaraju, A.K., Cell biology of prions and prionoids: a status report. Trends Cell Biol. 26 (2016), 40–51.
2. Alberti, S., Halfmann, R., King, O., Kapila, A., Lindquist, S., A systematic survey identifies prions and illuminates sequence features of prionogenic proteins. Cell 137 (2009), 146–158.
3. Altmeyer, M., Neelsen, K.J., Teloni, F., Pozdnyakova, I., Pellegrino, S., Grofte, M., Rask, M.B., Streicher, W., Jungmichel, S., Nielsen, M.L., Lukas, J., Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP-ribose). Nat. Commun., 6, 2015, 8088.
4. An, L., Fitzpatrick, D., Harrison, P.M., Emergence and evolution of yeast prion and prion-like proteins. BMC Evol. Biol., 16, 2016, 24.
5. Auluck, P.K., Chan, H.Y., Trojanowski, J.Q., Lee, V.M., Bonini, N.M., Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson׳s disease. Science 295 (2002), 865–868.
6. Ayala, Y.M., Pantano, S., D׳Ambrogio, A., Buratti, E., Brindisi, A., Marchetti, C., Romano, M., Baralle, F.E., Human, Drosophila, and C.elegans TDP43: nucleic acid binding properties and splicing regulatory function. J. Mol. Biol. 348 (2005), 575–588.
7. Balagopal, V., Parker, R., Polysomes, P bodies and stress granules: states and fates of eukaryotic mRNAs. Curr. Opin. Cell Biol. 21 (2009), 403–408.
8. Banfi, S., Servadio, A., Chung, M.Y., Kwiatkowski, T.J. Jr., McCall, A.E., Duvick, L.A., Shen, Y., Roth, E.J., Orr, H.T., Zoghbi, H.Y., Identification and characterization of the gene causing type 1 spinocerebellar ataxia. Nat. Genet. 7 (1994), 513–520.
9. Barmada, S.J., Skibinski, G., Korb, E., Rao, E.J., Wu, J.Y., Finkbeiner, S., Cytoplasmic mislocalization of TDP-43 is toxic to neurons and enhanced by a mutation associated with familial amyotrophic lateral sclerosis. J. Neurosci. 30 (2010), 639–649.
10. Baudin-Baillieu, A., Legendre, R., Kuchly, C., Hatin, I., Demais, S., Mestdagh, C., Gautheret, D., Namy, O., Genome-wide translational changes induced by the prion [PSI+]. Cell Rep. 8 (2014), 439–448.
11. Boisvert, F.M., van Koningsbruggen, S., Navascues, J., Lamond, A.I., The multifunctional nucleolus. Nat. Rev. Mol. Cell Biol. 8 (2007), 574–585.
12. Brangwynne, C.P., Phase transitions and size scaling of membrane-less organelles. J. Cell Biol. 203 (2013), 875–881.
13. Brangwynne, C.P., Eckmann, C.R., Courson, D.S., Rybarska, A., Hoege, C., Gharakhani, J., Julicher, F., Hyman, A.A., Germline P granules are liquid droplets that localize by controlled dissolution/condensation. Science 324 (2009), 1729–1732.
14. Brangwynne, Clifford, P., Tompa, P., Pappu, Rohit, V., Polymer physics of intracellular phase transitions. Nat. Phys. 11 (2015), 899–904.
15. Brettschneider, J., Arai, K., Del Tredici, K., Toledo, J.B., Robinson, J.L., Lee, E.B., Kuwabara, S., Shibuya, K., Irwin, D.J., Fang, L., Van Deerlin, V.M., Elman, L., McCluskey, L., Ludolph, A.C., Lee, V.M., Braak, H., Trojanowski, J.Q., TDP-43 pathology and neuronal loss in amyotrophic lateral sclerosis spinal cord. Acta Neuropathol. 128 (2014), 423–437.
16. Brettschneider, J., Del Tredici, K., Toledo, J.B., Robinson, J.L., Irwin, D.J., Grossman, M., Suh, E., Van Deerlin, V.M., Wood, E.M., Baek, Y., Kwong, L., Lee, E.B., Elman, L., McCluskey, L., Fang, L., Feldengut, S., Ludolph, A.C., Lee, V.M., Braak, H., Trojanowski, J.Q., Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Ann. Neurol. 74 (2013), 20–38.
17. Buchan, J.R., Kolaitis, R.M., Taylor, J.P., Parker, R., Eukaryotic stress granules are cleared by autophagy and Cdc48/VCP function. Cell 153 (2013), 1461–1474.
18. Buratti, E., Brindisi, A., Giombi, M., Tisminetzky, S., Ayala, Y.M., Baralle, F.E., 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. 280 (2005), 37572–37584.
19. Burke, K.A., Janke, A.M., Rhine, C.L., Fawzi, N.L., Residue-by-Residue View of In Vitro FUS Granules that Bind the C-Terminal Domain of RNA Polymerase II. Mol. Cell 60 (2015), 231–241.
20. Cherkasov, V., Hofmann, S., Druffel-Augustin, S., Mogk, A., Tyedmers, J., Stoecklin, G., Bukau, B., Coordination of translational control and protein homeostasis during severe heat stress. Curr. Biol. 23 (2013), 2452–2462.
21. Chernoff, Y.O., Galkin, A.P., Lewitin, E., Chernova, T.A., Newnam, G.P., Belenkiy, S.M., Evolutionary conservation of prion-forming abilities of the yeast Sup35 protein. Mol. Microbiol. 35 (2000), 865–876.
22. Chesi, A., Staahl, B.T., Jovicic, A., Couthouis, J., Fasolino, M., Raphael, A.R., Yamazaki, T., Elias, L., Polak, M., Kelly, C., Williams, K.L., Fifita, J.A., Maragakis, N.J., Nicholson, G.A., King, O.D., Reed, R., Crabtree, G.R., Blair, I.P., Glass, J.D., Gitler, A.D., Exome sequencing to identify de novo mutations in sporadic ALS trios. Nat. Neurosci. 16 (2013), 851–855.
23. Colby, D.W., Prusiner, S.B., Prions. Cold Spring Harb. Perspect. Biol., 3, 2011, a006833.
24. Collinge, J., Variant Creutzfeldt-Jakob disease. Lancet 354 (1999), 317–323.
25. Collinge, J., Clarke, A.R., A general model of prion strains and their pathogenicity. Science 318 (2007), 930–936.
26. Coschigano, P.W., Magasanik, B., The URE2 gene product of Saccharomyces cerevisiae plays an important role in the cellular response to the nitrogen source and has homology to glutathione s-transferases. Mol. Cell Biol. 11 (1991), 822–832.
27. Courchaine, E., Neugebauer, K.M., Paraspeckles: paragons of functional aggregation. J Cell Biol. 210 (2015), 527–528.
28. Couthouis, J., Raphael, A.R., Daneshjou, R., Gitler, A.D., Targeted exon capture and sequencing in sporadic amyotrophic lateral sclerosis. PLoS Genet., 10, 2014, e1004704.
29. Couthouis, J., Hart, M.P., Erion, R., King, O.D., Diaz, Z., Nakaya, T., Ibrahim, F., Kim, H.J., Mojsilovic-Petrovic, J., Panossian, S., Kim, C.E., Frackelton, E.C., Solski, J.A., Williams, K.L., Clay-Falcone, D., Elman, L., McCluskey, L., Greene, R., Hakonarson, H., Kalb, R.G., Lee, V.M., Trojanowski, J.Q., Nicholson, G.A., Blair, I.P., Bonini, N.M., Van Deerlin, V.M., Mourelatos, Z., Shorter, J., Gitler, A.D., Evaluating the role of the FUS/TLS-related gene EWSR1 in amyotrophic lateral sclerosis. Hum. Mol. Genet. 21 (2012), 2899–2911.
30. Couthouis, J., Hart, M.P., Shorter, J., DeJesus-Hernandez, M., Erion, R., Oristano, R., Liu, A.X., Ramos, D., Jethava, N., Hosangadi, D., Epstein, J., Chiang, A., Diaz, Z., Nakaya, T., Ibrahim, F., Kim, H.J., Solski, J.A., Williams, K.L., Mojsilovic-Petrovic, J., Ingre, C., Boylan, K., Graff-Radford, N.R., Dickson, D.W., Clay-Falcone, D., Elman, L., McCluskey, L., Greene, R., Kalb, R.G., Lee, V.M., Trojanowski, J.Q., Ludolph, A., Robberecht, W., Andersen, P.M., Nicholson, G.A., Blair, I.P., King, O.D., Bonini, N.M., Van Deerlin, V., Rademakers, R., Mourelatos, Z., Gitler, A.D., A yeast functional screen predicts new candidate ALS disease genes. Proc. Natl. Acad. Sci. USa 108 (2011), 20881–20890.
31. Cox, B.S., [PSI], a cytoplasmic suppressor of super-suppression in yeast. Heredity 20 (1965), 505–521.
32. Cummings, C.J., Mancini, M.A., Antalffy, B., DeFranco, D.B., Orr, H.T., Zoghbi, H.Y., Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein misfolding in SCA1. Nat. Genet. 19 (1998), 148–154.
33. Cushman, M., Johnson, B.S., King, O.D., Gitler, A.D., Shorter, J., Prion-like disorders: blurring the divide between transmissibility and infectivity. J. Cell Sci. 123 (2010), 1191–1201.
34. D׳Ambrogio, A., Buratti, E., Stuani, C., Guarnaccia, C., Romano, M., Ayala, Y.M., Baralle, F.E., Functional mapping of the interaction between TDP-43 and hnRNP A2 in vivo. Nucleic Acids Res. 37 (2009), 4116–4126.
35. Da Cruz, S., Cleveland, D.W., Understanding the role of TDP-43 and FUS/TLS in ALS and beyond. Curr. Opin. Neurobiol. 21 (2011), 904–919.
36. Derkatch, I.L., Liebman, S.W., The story of stolen chaperones: how overexpression of Q/N proteins cures yeast prions. Prion 7 (2013), 294–300.
37. DeSantis, M.E., Shorter, J., The elusive middle domain of Hsp104 and ClpB: location and function. Biochim. Biophys. Acta 1823 (2012), 29–39.
38. Dormann, D., Rodde, R., Edbauer, D., Bentmann, E., Fischer, I., Hruscha, A., Than, M.E., Mackenzie, I.R., Capell, A., Schmid, B., Neumann, M., Haass, C., ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import. EMBO J. 29 (2010), 2841–2857.
39. Du, Z., Zhang, Y., Li, L., The yeast prion [SWI(+)] abolishes multicellular growth by triggering conformational changes of multiple regulators required for flocculin gene expression. Cell Rep. 13 (2015), 2865–2878.
40. Edskes, H.K., Gray, V.T., Wickner, R.B., The [URE3] prion is an aggregated form of Ure2p that can be cured by overexpression of Ure2p fragments. Proc. Natl. Acad. Sci. USA 96 (1999), 1498–1503.
41. Elden, A.C., Kim, H.J., Hart, M.P., Chen-Plotkin, A.S., Johnson, B.S., Fang, X., Armakola, M., Geser, F., Greene, R., Lu, M.M., Padmanabhan, A., Clay-Falcone, D., McCluskey, L., Elman, L., Juhr, D., Gruber, P.J., Rub, U., Auburger, G., Trojanowski, J.Q., Lee, V.M., Van Deerlin, V.M., Bonini, N.M., Gitler, A.D., Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature 466 (2010), 1069–1075.
42. Erives, A.J., Fassler, J.S., Metabolic and chaperone gene loss marks the origin of animals: evidence for Hsp104 and Hsp78 chaperones sharing mitochondrial enzymes as clients. PLoS One, 10, 2015, e0117192.
43. Feiler, M.S., Strobel, B., Freischmidt, A., Helferich, A.M., Kappel, J., Brewer, B.M., Li, D., Thal, D.R., Walther, P., Ludolph, A.C., Danzer, K.M., Weishaupt, J.H., TDP-43 is intercellularly transmitted across axon terminals. J. Cell Biol. 211 (2015), 897–911.
44. Furukawa, Y., Kaneko, K., Watanabe, S., Yamanaka, K., Nukina, N., A seeding reaction recapitulates intracellular formation of Sarkosyl-insoluble transactivation response element (TAR) DNA-binding protein-43 inclusions. J. Biol. Chem. 286 (2011), 18664–18672.
45. Garcia, D.M., Jarosz, D.F., Rebels with a cause: molecular features and physiological consequences of yeast prions. FEMS Yeast Res. 14 (2014), 136–147.
46. Gitler, A.D., Shorter, J., RNA-binding proteins with prion-like domains in ALS and FTLD-U. Prion 5 (2011), 179–187.
47. Grad, L.I., Fernando, S.M., Cashman, N.R., From molecule to molecule and cell to cell: prion-like mechanisms in amyotrophic lateral sclerosis. Neurobiol. Dis. 77 (2015), 257–265.
48. Grishin, A.V., Rothenberg, M., Downs, M.A., Blumer, K.J., Mot3, a Zn finger transcription factor that modulates gene expression and attenuates mating pheromone signaling in Saccharomyces cerevisiae. Genetics 149 (1998), 879–892.
49. Guo, J.L., Lee, V.M., Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases. Nat. Med. 20 (2014), 130–138.
50. Guo, L., Shorter, J., It׳s raining liquids: RNA tunes viscoelasticity and dynamics of membraneless organelles. Mol. Cell 60 (2015), 189–192.
51. Guo, W., Chen, Y., Zhou, X., Kar, A., Ray, P., Chen, X., Rao, E.J., Yang, M., Ye, H., Zhu, L., Liu, J., Xu, M., Yang, Y., Wang, C., Zhang, D., Bigio, E.H., Mesulam, M., Shen, Y., Xu, Q., Fushimi, K., Wu, J.Y., An ALS-associated mutation affecting TDP-43 enhances protein aggregation, fibril formation and neurotoxicity. Nat. Struct. Mol. Biol. 18 (2011), 822–830.
52. Hackman, P., Sarparanta, J., Lehtinen, S., Vihola, A., Evila, A., Jonson, P.H., Luque, H., Kere, J., Screen, M., Chinnery, P.F., Ahlberg, G., Edstrom, L., Udd, B., Welander distal myopathy is caused by a mutation in the RNA-binding protein TIA1. Ann. Neurol. 73 (2013), 500–509.
53. Halfmann, R., Lindquist, S., Epigenetics in the extreme: prions and the inheritance of environmentally acquired traits. Science 330 (2010), 629–632.
54. Halfmann, R., Alberti, S., Lindquist, S., Prions, protein homeostasis, and phenotypic diversity. Trends Cell Biol. 20 (2010), 125–133.
55. Halfmann, R., Jarosz, D.F., Jones, S.K., Chang, A., Lancaster, A.K., Lindquist, S., Prions are a common mechanism for phenotypic inheritance in wild yeasts. Nature 482 (2012), 363–368.
56. Hennig, S., Kong, G., Mannen, T., Sadowska, A., Kobelke, S., Blythe, A., Knott, G.J., Iyer, K.S., Ho, D., Newcombe, E.A., Hosoki, K., Goshima, N., Kawaguchi, T., Hatters, D., Trinkle-Mulcahy, L., Hirose, T., Bond, C.S., Fox, A.H., Prion-like domains in RNA binding proteins are essential for building subnuclear paraspeckles. J. Cell Biol. 210 (2015), 529–539.
57. Holmes, D.L., Lancaster, A.K., Lindquist, S., Halfmann, R., Heritable remodeling of yeast multicellularity by an environmentally responsive prion. Cell 153 (2013), 153–165.
58. Hyman, A.A., Weber, C.A., Julicher, F., Liquid–liquid phase separation in biology. Annu. Rev. Cell Dev. Biol. 30 (2014), 39–58.
59. Jackrel, M.E., Shorter, J., Potentiated Hsp104 variants suppress toxicity of diverse neurodegenerative disease-linked proteins. Dis. Model. Mech. 7 (2014), 1175–1184.
60. Jackrel, M.E., Shorter, J., Reversing deleterious protein aggregation with re-engineered protein disaggregases. Cell Cycle 13 (2014), 1379–1383.
61. Jackrel, M.E., Shorter, J., Engineering enhanced protein disaggregases for neurodegenerative disease. Prion 9 (2015), 90–109.
62. Jackrel, M.E., Yee, K., Tariq, A., Chen, A.I., Shorter, J., Disparate mutations confer therapeutic gain of Hsp104 function. ACS Chem. Biol. 10 (2015), 2672–2679.
63. Jackrel, M.E., DeSantis, M.E., Martinez, B.A., Castellano, L.M., Stewart, R.M., Caldwell, K.A., Caldwell, G.A., Shorter, J., Potentiated Hsp104 variants antagonize diverse proteotoxic misfolding events. Cell 156 (2014), 170–182.
64. Jain, S., Wheeler, J.R., Walters, R.W., Agrawal, A., Barsic, A., Parker, R., ATPase-modulated stress granules contain a diverse proteome and substructure. Cell 164 (2016), 487–498.
65. Johnson, B.S., Snead, D., Lee, J.J., McCaffery, J.M., Shorter, J., Gitler, A.D., TDP-43 is intrinsically aggregation-prone, and amyotrophic lateral sclerosis-linked mutations accelerate aggregation and increase toxicity. J. Biol. Chem. 284 (2009), 20329–20339.
66. Johnson, J.O., Mandrioli, J., Benatar, M., Abramzon, Y., Van Deerlin, V.M., Trojanowski, J.Q., Gibbs, J.R., Brunetti, M., Gronka, S., Wuu, J., Ding, J., McCluskey, L., Martinez-Lage, M., Falcone, D., Hernandez, D.G., Arepalli, S., Chong, S., Schymick, J.C., Rothstein, J., Landi, F., Wang, Y.D., Calvo, A., Mora, G., Sabatelli, M., Monsurro, M.R., Battistini, S., Salvi, F., Spataro, R., Sola, P., Borghero, G., Consortium, I., Galassi, G., Scholz, S.W., Taylor, J.P., Restagno, G., Chio, A., Traynor, B.J., Exome sequencing reveals VCP mutations as a cause of familial ALS. Neuron 68 (2010), 857–864.
67. Ju, J.S., Fuentealba, R.A., Miller, S.E., Jackson, E., Piwnica-Worms, D., Baloh, R.H., Weihl, C.C., Valosin-containing protein (VCP) is required for autophagy and is disrupted in VCP disease. J. Cell Biol. 187 (2009), 875–888.
68. Kabashi, E., Lin, L., Tradewell, M.L., Dion, P.A., Bercier, V., Bourgouin, P., Rochefort, D., Bel Hadj, S., Durham, H.D., Vande Velde, C., Rouleau, G.A., Drapeau, P., Gain and loss of function of ALS-related mutations of TARDBP (TDP-43) cause motor deficits in vivo. Hum. Mol. Genet. 19 (2010), 671–683.
69. Kato, M., Han, T.W., Xie, S., Shi, K., Du, X., Wu, L.C., Mirzaei, H., Goldsmith, E.J., Longgood, J., Pei, J., Grishin, N.V., Frantz, D.E., Schneider, J.W., Chen, S., Li, L., Sawaya, M.R., Eisenberg, D., Tycko, R., McKnight, S.L., Cell-free formation of RNA granules: low complexity sequence domains form dynamic fibers within hydrogels. Cell 149 (2012), 753–767.
70. Kawaguchi, T., Hirose, T., Chromatin remodeling complexes in the assembly of long noncoding RNA-dependent nuclear bodies. Nucleus, 2015, 1–6.
71. Kawahara, Y., Mieda-Sato, A., TDP-43 promotes microRNA biogenesis as a component of the Drosha and Dicer complexes. Proc. Natl. Acad. Sci. USA 109 (2012), 3347–3352.
72. Kim, H.J., Kim, N.C., Wang, Y.D., Scarborough, E.A., Moore, J., Diaz, Z., MacLea, K.S., Freibaum, B., Li, S., Molliex, A., Kanagaraj, A.P., Carter, R., Boylan, K.B., Wojtas, A.M., Rademakers, R., Pinkus, J.L., Greenberg, S.A., Trojanowski, J.Q., Traynor, B.J., Smith, B.N., Topp, S., Gkazi, A.S., Miller, J., Shaw, C.E., Kottlors, M., Kirschner, J., Pestronk, A., Li, Y.R., Ford, A.F., Gitler, A.D., Benatar, M., King, O.D., Kimonis, V.E., Ross, E.D., Weihl, C.C., Shorter, J., Taylor, J.P., Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature 495 (2013), 467–473.
73. Kim, S.H., Shanware, N.P., Bowler, M.J., Tibbetts, R.S., Amyotrophic lateral sclerosis-associated proteins TDP-43 and FUS/TLS function in a common biochemical complex to co-regulate HDAC6 mRNA. J. Biol. Chem. 285 (2010), 34097–34105.
74. King, C.Y., Diaz-Avalos, R., Protein-only transmission of three yeast prion strains. Nature 428 (2004), 319–323.
75. King, O.D., Gitler, A.D., Shorter, J., The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease. Brain Res. 1462 (2012), 61–80.
76. Klar, J., Sobol, M., Melberg, A., Mabert, K., Ameur, A., Johansson, A.C., Feuk, L., Entesarian, M., Orlen, H., Casar-Borota, O., Dahl, N., Welander distal myopathy caused by an ancient founder mutation in TIA1 associated with perturbed splicing. Hum. Mutat. 34 (2013), 572–577.
77. Kraemer, B.C., Schuck, T., Wheeler, J.M., Robinson, L.C., Trojanowski, J.Q., Lee, V.M., Schellenberg, G.D., Loss of murine TDP-43 disrupts motor function and plays an essential role in embryogenesis. Acta Neuropathol. 119 (2010), 409–419.
78. Krick, R., Bremer, S., Welter, E., Schlotterhose, P., Muehe, Y., Eskelinen, E.L., Thumm, M., Cdc48/p97 and Shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like Atg8. J. Cell Biol. 190 (2010), 965–973.
79. Kroschwald, S., Maharana, S., Mateju, D., Malinovska, L., Nuske, E., Poser, I., Richter, D., Alberti, S., Promiscuous interactions and protein disaggregases determine the material state of stress-inducible RNP granules. Elife, 4, 2015, e06807.
80. Kryndushkin, D.S., Alexandrov, I.M., Ter-Avanesyan, M.D., Kushnirov, V.V., Yeast [PSI+] prion aggregates are formed by small Sup35 polymers fragmented by Hsp104. J. Biol. Chem. 278 (2003), 49636–49643.
81. Kwiatkowski, T.J. Jr., Bosco, D.A., Leclerc, A.L., Tamrazian, E., Vanderburg, C.R., Russ, C., Davis, A., Gilchrist, J., Kasarskis, E.J., Munsat, T., Valdmanis, P., Rouleau, G.A., Hosler, B.A., Cortelli, P., de Jong, P.J., Yoshinaga, Y., Haines, J.L., Pericak-Vance, M.A., Yan, J., Ticozzi, N., Siddique, T., McKenna-Yasek, D., Sapp, P.C., Horvitz, H.R., Landers, J.E., Brown, R.H. Jr., Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 323 (2009), 1205–1208.
82. Lancaster, A.K., Nutter-Upham, A., Lindquist, S., King, O.D., PLAAC: a web and command-line application to identify proteins with prion-like amino acid composition. Bioinformatics 30 (2014), 2501–2502.
83. Landsberg, M.J., Moran-Jones, K., Smith, R., Molecular recognition of an RNA trafficking element by heterogeneous nuclear ribonucleoprotein A2. Biochemistry 45 (2006), 3943–3951.
84. Lasagna-Reeves, C.A., Rousseaux, M.W., Guerrero-Munoz, M.J., Vilanova-Velez, L., Park, J., See, L., Jafar-Nejad, P., Richman, R., Orr, H.T., Kayed, R., Zoghbi, H.Y., Ataxin-1 oligomers induce local spread of pathology and decreasing them by passive immunization slows Spinocerebellar ataxia type 1 phenotypes. Elife, 4, 2015, e10891, 10.1016/j.jmb.2015.11.016.
85. Lee, B.J., Cansizoglu, A.E., Suel, K.E., Louis, T.H., Zhang, Z., Chook, Y.M., Rules for nuclear localization sequence recognition by karyopherin beta 2. Cell 126 (2006), 543–558.
86. Li, L., Lindquist, S., Creating a protein-based element of inheritance. Science 287 (2000), 661–664.
87. Li, P., Banjade, S., Cheng, H.C., Kim, S., Chen, B., Guo, L., Llaguno, M., Hollingsworth, J.V., King, D.S., Banani, S.F., Russo, P.S., Jiang, Q.X., Nixon, B.T., Rosen, M.K., Phase transitions in the assembly of multivalent signalling proteins. Nature 483 (2012), 336–340.
88. Li, Y., Ray, P., Rao, E.J., Shi, C., Guo, W., Chen, X., Woodruff, E.A. 3rd, Fushimi, K., Wu, J.Y., A Drosophila model for TDP-43 proteinopathy. Proc. Natl. Acad. Sci. USA 107 (2010), 3169–3174.
89. Li, Y.R., King, O.D., Shorter, J., Gitler, A.D., Stress granules as crucibles of ALS pathogenesis. J. Cell Biol. 201 (2013), 361–372.
90. Liebman, S.W., Chernoff, Y.O., Prions in yeast. Genetics 191 (2012), 1041–1072.
91. Lim, L., Wei, Y., Lu, Y., Song, J., ALS-causing mutations significantly perturb the self-assembly and interaction with nucleic acid of the intrinsically disordered prion-like domain of TDP-43. PLoS Biol., 14, 2016, e1002338.
92. Lin, Y., Protter, D.S., Rosen, M.K., Parker, R., Formation and maturation of phase-separated liquid droplets by RNA-binding proteins. Mol. Cell 60 (2015), 208–219.
93. Lindquist, S., Mad cows meet psi-chotic yeast: the expansion of the prion hypothesis. Cell 89 (1997), 495–498.
94. Ling, S.C., Polymenidou, M., Cleveland, D.W., Converging mechanisms in ALS and FTD: disrupted RNA and protein homeostasis. Neuron 79 (2013), 416–438.
95. Ludolph, A.C., Brettschneider, J., TDP-43 in amyotrophic lateral sclerosis - is it a prion disease?. Eur. J. Neurol. 22 (2015), 753–761.
96. Luk, K.C., Kehm, V., Carroll, J., Zhang, B., O׳Brien, P., Trojanowski, J.Q., Lee, V.M., Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 338 (2012), 949–953.
97. Ma, J., Wang, F., Prion disease and the ‘protein-only hypothesis’. Essays Biochem. 56 (2014), 181–191.
98. Maniecka, Z., Polymenidou, M., From nucleation to widespread propagation: a prion-like concept for ALS. Virus Res. 207 (2015), 94–105.
99. Masel, J., Bergman, A., The evolution of the evolvability properties of the yeast prion [PSI+]. Evolution 57 (2003), 1498–1512.
100. Masel, J., Siegal, M.L., Robustness: mechanisms and consequences. Trends Genet. 25 (2009), 395–403.
101. Mayeda, A., Munroe, S.H., Caceres, J.F., Krainer, A.R., Function of conserved domains of hnRNP A1 and other hnRNP A/B proteins. EMBO J. 13 (1994), 5483–5495.
102. McGlinchey, R.P., Kryndushkin, D., Wickner, R.B., Suicidal [PSI+] is a lethal yeast prion. Proc. Natl. Acad. Sci. USA 108 (2011), 5337–5341.
103. Meyer, H., Bug, M., Bremer, S., Emerging functions of the VCP/p97 AAA-ATPase in the ubiquitin system. Nat. Cell Biol. 14 (2012), 117–123.
104. Michelitsch, M.D., Weissman, J.S., A census of glutamine/asparagine-rich regions: implications for their conserved function and the prediction of novel prions. Proc. Natl. Acad. Sci. USA 97 (2000), 11910–11915.
105. Molliex, A., Temirov, J., Lee, J., Coughlin, M., Kanagaraj, A.P., Kim, H.J., Mittag, T., Taylor, J.P., Phase separation by low complexity domains promotes stress granule assembly and drives pathological fibrillization. Cell 163 (2015), 123–133.
106. Mori, K., Lammich, S., Mackenzie, I.R., Forne, I., Zilow, S., Kretzschmar, H., Edbauer, D., Janssens, J., Kleinberger, G., Cruts, M., 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. 125 (2013), 413–423.
107. Murakami, T., Qamar, S., Lin, J.Q., Schierle, G.S., Rees, E., Miyashita, A., Costa, A.R., Dodd, R.B., Chan, F.T., Michel, C.H., Kronenberg-Versteeg, D., Li, Y., Yang, S.P., Wakutani, Y., Meadows, W., Ferry, R.R., Dong, L., Tartaglia, G.G., Favrin, G., Lin, W.L., Dickson, D.W., Zhen, M., Ron, D., Schmitt-Ulms, G., Fraser, P.E., Shneider, N.A., Holt, C., Vendruscolo, M., Kaminski, C.F., St George-Hyslop, P., ALS/FTD mutation-induced phase transition of FUS liquid droplets and reversible hydrogels into irreversible hydrogels impairs rnp granule function. Neuron 88 (2015), 678–690.
108. Nakayashiki, T., Kurtzman, C.P., Edskes, H.K., Wickner, R.B., Yeast prions [URE3] and [PSI+] are diseases. Proc. Natl. Acad. Sci. USA 102 (2005), 10575–10580.
109. Namy, O., Galopier, A., Martini, C., Matsufuji, S., Fabret, C., Rousset, J.P., Epigenetic control of polyamines by the prion [PSI+]. Nat. Cell Biol. 10 (2008), 1069–1075.
110. Neumann, M., Sampathu, D.M., Kwong, L.K., Truax, A.C., Micsenyi, M.C., Chou, T.T., Bruce, J., Schuck, T., Grossman, M., Clark, C.M., McCluskey, L.F., Miller, B.L., Masliah, E., Mackenzie, I.R., Feldman, H., Feiden, W., Kretzschmar, H.A., Trojanowski, J.Q., Lee, V.M., Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314 (2006), 130–133.
111. Newby, G.A., Lindquist, S., Blessings in disguise: biological benefits of prion-like mechanisms. Trends Cell Biol. 23 (2013), 251–259.
112. Nillegoda, N.B., Bukau, B., Metazoan Hsp70-based protein disaggregases: emergence and mechanisms. Front. Mol. Biosci., 2, 2015, 57.
113. Nonaka, T., Masuda-Suzukake, M., Arai, T., Hasegawa, Y., Akatsu, H., Obi, T., Yoshida, M., Murayama, S., Mann, D.M., Akiyama, H., Hasegawa, M., Prion-like properties of pathological TDP-43 aggregates from diseased brains. Cell Rep. 4 (2013), 124–134.
114. Orr, H.T., Cell biology of spinocerebellar ataxia. J. Cell Biol. 197 (2012), 167–177.
115. Orr, H.T., Zoghbi, H.Y., Trinucleotide repeat disorders. Annu. Rev. Neurosci. 30 (2007), 575–621.
116. Osherovich, L.Z., Weissman, J.S., Multiple Gln/Asn-rich prion domains confer susceptibility to induction of the yeast [PSI+] prion. Cell 106 (2001), 183–194.
117. Patel, A., Lee, Hyun, O., Jawerth, L., Maharana, S., Jahnel, M., Hein, Marco, Y., Stoynov, S., Mahamid, J., Saha, S., Franzmann, Titus, M., Pozniakovski, A., Poser, I., Maghelli, N., Royer, Loic, A., Weigert, M., Myers, Eugene, W., Grill, S., Drechsel, D., Hyman, Anthony, A., Alberti, S., A liquid-to-solid phase transition of the ALS protein FUS accelerated by disease mutation. Cell 162 (2015), 1066–1077.
118. Paul, K.R., Hendrich, C.G., Waechter, A., Harman, M.R., Ross, E.D., Generating new prions by targeted mutation or segment duplication. Proc. Natl. Acad. Sci. USA 112 (2015), 8584–8589.
119. Polymenidou, M., Cleveland, D.W., The seeds of neurodegeneration: prion-like spreading in ALS. Cell 147 (2011), 498–508.
120. Polymenidou, M., Cleveland, D.W., Prion-like spread of protein aggregates in neurodegeneration. J. Exp. Med. 209 (2012), 889–893.
121. Prusiner, S.B., Prions. Proc. Natl. Acad. Sci. USA 95 (1998), 13363–13383.
122. Ramaswami, M., Taylor, J.P., Parker, R., Altered ribostasis: RNA-protein granules in degenerative disorders. Cell 154 (2013), 727–736.
123. Ravits, J.M., La Spada, A.R., ALS motor phenotype heterogeneity, focality, and spread: deconstructing motor neuron degeneration. Neurology 73 (2009), 805–811.
124. Resende, C.G., Outeiro, T.F., Sands, L., Lindquist, S., Tuite, M.F., Prion protein gene polymorphisms in Saccharomyces cerevisiae. Mol. Microbiol. 49 (2003), 1005–1017.
125. Ritson, G.P., Custer, S.K., Freibaum, B.D., Guinto, J.B., Geffel, D., Moore, J., Tang, W., Winton, M.J., Neumann, M., Trojanowski, J.Q., Lee, V.M., Forman, M.S., Taylor, J.P., TDP-43 mediates degeneration in a novel Drosophila model of disease caused by mutations in VCP/p97. J. Neurosci. 30 (2010), 7729–7739.
126. Roberts, B.E., Duennwald, M.L., Wang, H., Chung, C., Lopreiato, N.P., Sweeny, E.A., Knight, M.N., Shorter, J., A synergistic small-molecule combination directly eradicates diverse prion strain structures. Nat. Chem. Biol. 5 (2009), 936–946.
127. Ross, E.D., Baxa, U., Wickner, R.B., Scrambled prion domains form prions and amyloid. Mol. Cell Biol. 24 (2004), 7206–7213.
128. Ross, E.D., Edskes, H.K., Terry, M.J., Wickner, R.B., Primary sequence independence for prion formation. Proc. Natl. Acad. Sci. USA 102 (2005), 12825–12830.
129. Santoso, A., Chien, P., Osherovich, L.Z., Weissman, J.S., Molecular basis of a yeast prion species barrier. Cell 100 (2000), 277–288.
130. Satpute-Krishnan, P., Langseth, S.X., Serio, T.R., Hsp104-dependent remodeling of prion complexes mediates protein-only inheritance. PLoS Biol., 5, 2007, e24.
131. Sephton, C.F., Good, S.K., Atkin, S., Dewey, C.M., Mayer, P. 3rd, Herz, J., Yu, G., TDP-43 is a developmentally regulated protein essential for early embryonic development. J. Biol. Chem. 285 (2010), 6826–6834.
132. Serio, T.R., Cashikar, A.G., Kowal, A.S., Sawicki, G.J., Moslehi, J.J., Serpell, L., Arnsdorf, M.F., Lindquist, S.L., Nucleated conformational conversion and the replication of conformational information by a prion determinant. Science 289 (2000), 1317–1321.
133. Seydoux, G., Braun, R.E., Pathway to totipotency: lessons from germ cells. Cell 127 (2006), 891–904.
134. Shorter, J., Hsp104: a weapon to combat diverse neurodegenerative disorders. Neurosignals 16 (2008), 63–74.
135. Shorter, J., Emergence and natural selection of drug-resistant prions. Mol. Biosyst. 6 (2010), 1115–1130.
136. Shorter, J., The mammalian disaggregase machinery: Hsp110 synergizes with Hsp70 and Hsp40 to catalyze protein disaggregation and reactivation in a cell-free system. PLoS One, 6, 2011, e26319.
137. Shorter, J., Lindquist, S., Hsp104 catalyzes formation and elimination of self-replicating Sup35 prion conformers. Science 304 (2004), 1793–1797.
138. Shorter, J., Lindquist, S., Prions as adaptive conduits of memory and inheritance. Nat. Rev. Genet. 6 (2005), 435–450.
139. Shorter, J., Lindquist, S., Destruction or potentiation of different prions catalyzed by similar Hsp104 remodeling activities. Mol. Cell 23 (2006), 425–438.
140. Shorter, J., Lindquist, S., Hsp104, Hsp70 and Hsp40 interplay regulates formation, growth and elimination of Sup35 prions. EMBO J. 27 (2008), 2712–2724.
141. Shorter, J., Taylor, J.P., Disease mutations in the prion-like domains of hnRNPA1 and hnRNPA2/B1 introduce potent steric zippers that drive excess RNP granule assembly. Rare Dis., 1, 2013, e25200.
142. Sondheimer, N., Lindquist, S., Rnq1: an epigenetic modifier of protein function in yeast. Mol. Cell 5 (2000), 163–172.
143. Sreedharan, J., Blair, I.P., Tripathi, V.B., Hu, X., Vance, C., Rogelj, B., Ackerley, S., Durnall, J.C., Williams, K.L., Buratti, E., Baralle, F., de Belleroche, J., Mitchell, J.D., Leigh, P.N., Al-Chalabi, A., Miller, C.C., Nicholson, G., Shaw, C.E., TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319 (2008), 1668–1672.
144. Strome, S., Lehmann, R., Germ versus soma decisions: lessons from flies and worms. Science 316 (2007), 392–393.
145. Suel, K.E., Gu, H., Chook, Y.M., Modular organization and combinatorial energetics of proline-tyrosine nuclear localization signals. PLoS Biol., 6, 2008, e137.
146. Sun, Z., Diaz, Z., Fang, X., Hart, M.P., Chesi, A., Shorter, J., Gitler, A.D., Molecular determinants and genetic modifiers of aggregation and toxicity for the ALS disease protein FUS/TLS. PLoS Biol., 9, 2011, e1000614.
147. Suzuki, G., Tanaka, M., Expanding the yeast prion world: active prion conversion of non-glutamine/asparagine-rich Mod5 for cell survival. Prion 7 (2013), 109–113.
148. Suzuki, G., Shimazu, N., Tanaka, M., A yeast prion, Mod5, promotes acquired drug resistance and cell survival under environmental stress. Science 336 (2012), 355–359.
149. Sweeny, E.A., Shorter, J., Prion proteostasis: Hsp104 meets its supporting cast. Prion 2 (2008), 135–140.
150. Sweeny, E.A., Shorter, J., Mechanistic and Structural Insights into the Prion-Disaggregase Activity of Hsp104. J. Mol. Biol., 2015, 10.1016/j.jmb.2015.11.016.
151. Sweeny, E.A., Jackrel, M.E., Go, M.S., Sochor, M.A., Razzo, B.M., DeSantis, M.E., Gupta, K., Shorter, J., The Hsp104 N-terminal domain enables disaggregase plasticity and potentiation. Mol. Cell 57 (2015), 836–849.
152. Tanaka, M., Chien, P., Naber, N., Cooke, R., Weissman, J.S., Conformational variations in an infectious protein determine prion strain differences. Nature 428 (2004), 323–328.
153. Ter-Avanesyan, M.D., Kushnirov, V.V., Dagkesamanskaya, A.R., Didichenko, S.A., Chernoff, Y.O., Inge-Vechtomov, S.G., Smirnov, V.N., Deletion analysis of the SUP35 gene of the yeast Saccharomyces cerevisiae reveals two non-overlapping functional regions in the encoded protein. Mol. Microbiol. 7 (1993), 683–692.
154. Toombs, J.A., McCarty, B.R., Ross, E.D., Compositional determinants of prion formation in yeast. Mol. Cell Biol. 30 (2010), 319–332.
155. Toombs, J.A., Petri, M., Paul, K.R., Kan, G.Y., Ben-Hur, A., Ross, E.D., De novo design of synthetic prion domains. Proc. Natl. Acad. Sci. USA 109 (2012), 6519–6524.
156. Torrente, M.P., Shorter, J., The metazoan protein disaggregase and amyloid depolymerase system: Hsp110, Hsp70, Hsp40, and small heat shock proteins. Prion 7 (2013), 457–463.
157. Torrente, M.P., Chuang, E., Noll, M.M., Jackrel, M.E., Go, M.S., Shorter, J., Mechanistic Insights Into Hsp104 Potentiation. J Biol. Chem. 291 (2016), 5101–5115.
158. True, H.L., Lindquist, S.L., A yeast prion provides a mechanism for genetic variation and phenotypic diversity. Nature 407 (2000), 477–483.
159. True, H.L., Berlin, I., Lindquist, S.L., Epigenetic regulation of translation reveals hidden genetic variation to produce complex traits. Nature 431 (2004), 184–187.
160. Tuite, M.F., Serio, T.R., The prion hypothesis: from biological anomaly to basic regulatory mechanism. Nat. Rev. Mol. Cell Biol. 11 (2010), 823–833.
161. Tuite, M.F., Staniforth, G.L., Cox, B.S., [PSI(+)] turns 50. Prion 9 (2015), 318–332.
162. Tyedmers, J., Madariaga, M.L., Lindquist, S., Prion switching in response to environmental stress. PLoS Biol., 6, 2008, e294.
163. Tyedmers, J., Treusch, S., Dong, J., McCaffery, J.M., Bevis, B., Lindquist, S., Prion induction involves an ancient system for the sequestration of aggregated proteins and heritable changes in prion fragmentation. Proc. Natl. Acad. Sci. USA 107 (2010), 8633–8638.
164. Vance, C., Rogelj, B., Hortobagyi, T., De Vos, K.J., Nishimura, A.L., Sreedharan, J., Hu, X., Smith, B., Ruddy, D., Wright, P., Ganesalingam, J., Williams, K.L., Tripathi, V., Al-Saraj, S., Al-Chalabi, A., Leigh, P.N., Blair, I.P., Nicholson, G., de Belleroche, J., Gallo, J.M., Miller, C.C., Shaw, C.E., Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323 (2009), 1208–1211.
165. Vieira, N.M., Naslavsky, M.S., Licinio, L., Kok, F., Schlesinger, D., Vainzof, M., Sanchez, N., Kitajima, J.P., Gal, L., Cavacana, N., Serafini, P.R., Chuartzman, S., Vasquez, C., Mimbacas, A., Nigro, V., Pavanello, R.C., Schuldiner, M., Kunkel, L.M., Zatz, M., A defect in the RNA-processing protein HNRPDL causes limb-girdle muscular dystrophy 1G (LGMD1G). Hum. Mol. Genet. 23 (2014), 4103–4110.
166. Walters, R.W., Muhlrad, D., Garcia, J., Parker, R., Differential effects of Ydj1 and Sis1 on Hsp70-mediated clearance of stress granules in Saccharomyces cerevisiae. RNA 21 (2015), 1660–1671.
167. Wang, F., Wang, X., Ma, J., Conversion of bacterially expressed recombinant prion protein. Methods 53 (2011), 208–213.
168. Wang, F., Wang, X., Yuan, C.G., Ma, J., Generating a prion with bacterially expressed recombinant prion protein. Science 327 (2010), 1132–1135.
169. Wang, F., Zhang, Z., Wang, X., Li, J., Zha, L., Yuan, C.G., Weissmann, C., Ma, J., Genetic informational RNA is not required for recombinant prion infectivity. J. Virol. 86 (2011), 1874–1876.
170. Wang, T., Birsoy, K., Hughes, N.W., Krupczak, K.M., Post, Y., Wei, J.J., Lander, E.S., Sabatini, D.M., Identification and characterization of essential genes in the human genome. Science 350 (2015), 1096–1101.
171. Weber, S.C., Brangwynne, C.P., Getting RNA and protein in phase. Cell 149 (2012), 1188–1191.
172. Weber, S.C., Brangwynne, C.P., Inverse size scaling of the nucleolus by a concentration-dependent phase transition. Curr. Biol. 25 (2015), 641–646.
173. Wickner, R.B., [URE3] as an altered URE2 protein: evidence for a prion analog in Saccharomyces cerevisiae. Science 264 (1994), 566–569.
174. Wickner, R.B., Edskes, H.K., Bateman, D., Kelly, A.C., Gorkovskiy, A., The yeast prions [PSI+] and [URE3] are molecular degenerative diseases. Prion 5 (2011), 258–262.
175. Wickner, R.B., Shewmaker, F.P., Bateman, D.A., Edskes, H.K., Gorkovskiy, A., Dayani, Y., Bezsonov, E.E., Yeast prions: structure, biology, and prion-handling systems. Microbiol. Mol. Biol. Rev. 79 (2015), 1–17.
176. Xiang, S., Kato, M., Wu, L.C., Lin, Y., Ding, M., Zhang, Y., Yu, Y., McKnight, S.L., The LC domain of hnRNPA2 adopts similar conformations in hydrogel polymers, liquid-like droplets, and nuclei. Cell 163 (2015), 829–839.
177. Yu, A., Shibata, Y., Shah, B., Calamini, B., Lo, D.C., Morimoto, R.I., Protein aggregation can inhibit clathrin-mediated endocytosis by chaperone competition. Proc. Natl. Acad. Sci. USA 111 (2014), E1481–E1490.
178. Zhang, H., Elbaum-Garfinkle, S., Langdon, E.M., Taylor, N., Occhipinti, P., Bridges, A.A., Brangwynne, C.P., Gladfelter, A.S., RNA Controls PolyQ Protein Phase Transitions. Mol. Cell 60 (2015), 220–230.
179. Zhang, Y.J., Xu, Y.F., Cook, C., Gendron, T.F., Roettges, P., Link, C.D., Lin, W.L., Tong, J., Castanedes-Casey, M., Ash, P., Gass, J., Rangachari, V., Buratti, E., Baralle, F., Golde, T.E., Dickson, D.W., Petrucelli, L., Aberrant cleavage of TDP-43 enhances aggregation and cellular toxicity. Proc. Natl. Acad. Sci. USA 106 (2009), 7607–7612.
180. Zhang, Z.C., Chook, Y.M., Structural and energetic basis of ALS-causing mutations in the atypical proline-tyrosine nuclear localization signal of the Fused in Sarcoma protein (FUS). Proc. Natl. Acad. Sci. USA 109 (2012), 12017–12021.
181. Zhu, L., Brangwynne, C.P., Nuclear bodies: the emerging biophysics of nucleoplasmic phases. Curr. Opin. Cell Biol. 34 (2015), 23–30.
182. Zoghbi, H.Y., Orr, H.T., Pathogenic mechanisms of a polyglutamine-mediated neurodegenerative disease, spinocerebellar ataxia type 1. J. Biol. Chem. 284 (2009), 7425–7429.