This review article aims at comprehensive understanding of biological functions of RNA-binding proteins (RBPs) and cognate RNAs. For showing the divergent and dispersed aspects of RBP functions of the human genome in living cells, RBP TLS/FUS is chosen for these topics. Recent discovery of TLS as a phase transition or phase separation inducer presents previously unprecedented models regarding phase separation and enhancer functions in the genome. Trends in research altered up to interests or desire of scientists. Research activities of TLS/FUS have been dramatically drifted across over the last century. TLS was identified as a fusion gene product of TLS-CHOP of liposarcoma in 1993. Before announcement of the human genome draft, there were compelling desires to hunt novel genes. Gene cloning from libraries was one of prevalent activities at that time. Next wave came with describing TLS as a causative gene for familial amyotrophic lateral sclerosis (ALS). Investigation of lethal neurodegenerative disease, ALS has social impact. Elucidation of onset of ALS has progressed rapidly. Latest discovery with TLS is its solute for phase separation and phase transition into aggregation. The phase separation and resultant aggregation are pointed out in relation to the onset of ALS. Then, people rush to search for tide of TLS to phase separation in link to cause for ALS. Analysis of the phase separation could provide a novel outline for long distant regulation of gene in the genome. In this review article, the author focuses emerging trendy targets of a versatile molecule TLS and discuss scientific needs behind these orientation for a specific molecule in biological sciences.
| Published in | Biomedical Sciences (Volume 6, Issue 1) |
| DOI | 10.11648/j.bs.20200601.12 |
| Page(s) | 5-16 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2024. Published by Science Publishing Group |
RNA-binding Proteins, TLS/FUS, Liposarcoma, Amyotrophic Lateral Sclerosis, Phase Separation, Phase Transition, Intrinsically Disordered region, Low Complexity Domain, Nuclear Condensate
| [1] | Knight JC, Renwick PJ, Dal Cin P, et al. Translocation t (12; 16) (q13; p11) in Myxoid Liposarcoma and Round Cell Liposarcoma: Molecular and Cytogenetic Analysis. Cancer Research. 1995; 55 (1): 24-27. |
| [2] | Pérez-Losada J, Sánchez-Martín M, Rodríguez-García MA, et al. Liposarcoma initiated by FUS/TLS-CHOP: the FUS/TLS domain plays a critical role in the pathogenesis of liposarcoma. Oncogene. 2000 2000/12/01; 19 (52): 6015-6022. |
| [3] | Crozat A, Aman P, Mandahl N, et al. Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. Nature. 1993 Jun 17; 363 (6430): 640-4. |
| [4] | Zinszner H, Albalat R, Ron D. A novel effector domain from the RNA-binding protein TLS or EWS is required for oncogenic transformation by CHOP. Genes Dev. 1994 Nov 1; 8 (21): 2513-26. |
| [5] | Antonescu CR, Elahi A, Humphrey M, et al. Specificity of TLS-CHOP rearrangement for classic myxoid/round cell liposarcoma: absence in predominantly myxoid well-differentiated liposarcomas. J Mol Diagn. 2000 Aug; 2 (3): 132-8. |
| [6] | Antonescu CR, Tschernyavsky SJ, Decuseara R, et al. Prognostic impact of P53 status, TLS- CHOP fusion transcript structure, and histological grade in myxoid liposarcoma: a molecular and clinicopathologic study of 82 cases. Clin Cancer Res. 2001 Dec; 7 (12): 3977-87. |
| [7] | Perez-Mancera PA, Perez-Losada J, Sanchez-Martin M, et al. Expression of the FUS domain restores liposarcoma development in CHOP transgenic mice. Oncogene. 2002 Mar 7; 21 (11): 1679-84. |
| [8] | Delattre O, Zucman J, Plougastel B, et al. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature. 1992 Sep 10; 359 (6391): 162-5. |
| [9] | Bertolotti A, Bell B, Tora L. The N-terminal domain of human TAFII68 displays transactivation and oncogenic properties. Oncogene. 1999 Dec 23; 18 (56): 8000-10. |
| [10] | Attwooll C, Tariq M, Harris M, et al. Identification of a novel fusion gene involving hTAFII68 and CHN from a t (9; 17) (q22; q11.2) translocation in an extraskeletal myxoid chondrosarcoma. Oncogene. 1999 Dec 9; 18 (52): 7599-601. |
| [11] | Kato M, Han TW, Xie S, et al. Cell-free formation of RNA granules: low complexity sequence domains form dynamic fibers within hydrogels. Cell. 2012 May 11; 149 (4): 753-67. |
| [12] | Evans RM. The steroid and thyroid hormone receptor superfamily. Science. 1988 May 13; 240 (4854): 889-95. |
| [13] | Mangelsdorf DJ, Thummel C, Beato M, et al. The nuclear receptor superfamily: The second decade. Cell. 1995 1995/12/15/; 83 (6): 835-839. |
| [14] | Glass CK, Rosenfeld MG. The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev. 2000 Jan 15; 14 (2): 121-41. |
| [15] | Kurokawa R, DiRenzo J, Boehm M, et al. Regulation of retinoid signalling by receptor polarity and allosteric control of ligand binding. Nature. 1994 Oct 6; 371 (6497): 528-31. |
| [16] | Rosenfeld MG, Lunyak VV, Glass CK. Sensors and signals: a coactivator/corepressor/epigenetic code for integrating signal-dependent programs of transcriptional response. Genes & development. 2006; 20 (11): 1405-1428. |
| [17] | Kamei Y, Xu L, Heinzel T, et al. A CBP integrator complex mediates transcriptional activation. |
| [18] | Kurokawa R, Kalafus D, Ogliastro MH, et al. Differential use of CREB binding protein-coactivator complexes. Science. 1998 Jan 30; 279 (5351): 700-3. |
| [19] | Korzus E, Torchia J, Rose DW, et al. Transcription factor-specific requirements for coactivators and their acetyltransferase functions. Science. 1998 Jan 30; 279 (5351): 703-7. |
| [20] | Kurokawa R, Soderstrom M, Horlein A, et al. Polarity-specific activities of retinoic acid receptors determined by a co-repressor. Nature. 1995 Oct 5; 377 (6548): 451-4. |
| [21] | Horlein AJ, Naar AM, Heinzel T, et al. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature. 1995 Oct 5; 377 (6548): 397-404. |
| [22] | Chen JD, Evans RM. A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature. 1995 Oct 5; 377 (6548): 454-7. |
| [23] | Powers CA, Mathur M, Raaka BM, et al. TLS (translocated-in-liposarcoma) is a high-affinity interactor for steroid, thyroid hormone, and retinoid receptors. Mol Endocrinol. 1998 Jan; 12 (1): 4-18. |
| [24] | Wang X, Arai S, Song X, et al. Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription. Nature. 2008 Jul 3; 454 (7200): 126-30. |
| [25] | Yoneda R, Suzuki S, Mashima T, et al. The binding specificity of Translocated in LipoSarcoma/FUsed in Sarcoma with lncRNA transcribed from the promoter region of cyclin D1. Cell & bioscience. 2016; 6: 4. |
| [26] | Cui W, Yoneda R, Ueda N, et al. Arginine methylation of translocated in liposarcoma (TLS) inhibits its binding to long noncoding RNA, abrogating TLS-mediated repression of CBP/p300 activity. J Biol Chem. 2018 Jul 13; 293 (28): 10937-10948. |
| [27] | Lerga A, Hallier M, Delva L, et al. Identification of an RNA binding specificity for the potential splicing factor TLS. J Biol Chem. 2001 Mar 2; 276 (9): 6807-16. |
| [28] | Kurokawa R, Rosenfeld MG, Glass CK. Transcriptional regulation through noncoding RNAs and epigenetic modifications. RNA Biol. 2009 Jul; 6 (3): 233-6. |
| [29] | Kurokawa R. Promoter-associated long noncoding RNAs repress transcription through a RNA binding protein TLS. Advances in experimental medicine and biology. 2011; 722: 196-208. |
| [30] | Kurokawa R. Long noncoding RNA as a regulator for transcription. Prog Mol Subcell Biol. 2011; 51: 29-41. |
| [31] | Kurokawa R. Generation of Functional Long Noncoding RNA Through Transcription and Natural Selection. Regulatory RNAs: Springer; 2012. p. 151-174. |
| [32] | Kurokawa R, editor. Long Noncoding RNAs: Springer; 2015. |
| [33] | Kurokawa R. Initiation of Transcription Generates Divergence of Long Noncoding RNAs. Long Noncoding RNAs: Springer; 2015. p. 69-91. |
| [34] | Yamanaka K, Chun SJ, Boillee S, et al. Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. Nature Neuroscience. 2008 2008/03/01; 11 (3): 251-253. |
| [35] | Lagier-Tourenne C, Cleveland DW. Rethinking ALS: the FUS about TDP-43. Cell. 2009 Mar 20; 136 (6): 1001-4. |
| [36] | Lagier-Tourenne C, Polymenidou M, Cleveland DW. TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration. Hum Mol Genet. 2010 Apr 15; 19 (R1): R46-64. |
| [37] | Da Cruz S, Cleveland DW. Understanding the role of TDP-43 and FUS/TLS in ALS and beyond. Current Opinion in Neurobiology. 2011 2011/12/01/; 21 (6): 904-919. |
| [38] | Lagier-Tourenne C, Polymenidou M, Hutt KR, et al. Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs. Nature Neuroscience. 2012; 15: 1488. |
| [39] | Rosen DR, Siddique T, Patterson D, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993 Mar 04; 362 (6415): 59-62. |
| [40] | Lafon-Cazal M, Pietri S, Culcasi M, et al. NMDA-dependent superoxide production and neurotoxicity. Nature. 1993 1993/08/01; 364 (6437): 535-537. |
| [41] | Beckman JS, Carson M, Smith CD, et al. ALS, SOD and peroxynitrite. Nature. 1993 1993/08/01; 364 (6438): 584-584. |
| [42] | Vance C, Rogelj B, Hortobagyi T, et al. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science. 2009 Feb 27; 323 (5918): 1208-11. |
| [43] | Kwiatkowski TJ, Jr., Bosco DA, Leclerc AL, et al. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science. 2009 Feb 27; 323 (5918): 1205-8. |
| [44] | Gal J, Zhang J, Kwinter DM, et al. Nuclear localization sequence of FUS and induction of stress granules by ALS mutants. Neurobiology of Aging. 2011 2011/12/01/; 32 (12): 2323. e27-2323. e40. |
| [45] | Kurokawa R, Bando T. Three-Dimensional Structure of RNA-Binding Protein TLS Co- Crystallized with Biotinylated Isoxazole. Biomedical Sciences. 2016; 2: 1-10. |
| [46] | Ueda N, Kashiwazaki G, Bando T, et al. Biotin-Lys-His Blocks Aggregation of RNA-binding Protein TLS, a Cause of Amyotrophic Lateral Sclerosis. Biomedical Sciences. 2017; 3 (4): 67-77. |
| [47] | Lorković ZJ, Barta A. Genome analysis: RNA recognition motif (RRM) and K homology (KH) domain RNA-binding proteins from the flowering plant Arabidopsis thaliana. Nucleic Acids Research. 2002; 30 (3): 623-635. |
| [48] | Farina KL, Hüttelmaier S, Musunuru K, et al. Two ZBP1 KH domains facilitate β-actin mRNA localization, granule formation, and cytoskeletal attachment. J Cell Biol. 2003; 160 (1): 77-87. |
| [49] | Han TW, Kato M, Xie S, et al. Cell-free formation of RNA granules: bound RNAs identify features and components of cellular assemblies. Cell. 2012 May 11; 149 (4): 768-79. |
| [50] | Gerstberger S, Hafner M, Tuschl T. A census of human RNA-binding proteins. Nature Reviews Genetics. 2014; 15: 829. |
| [51] | Patel A, Lee Hyun O, Jawerth L, et al. A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease Mutation. Cell. 2015; 162 (5): 1066-1077. |
| [52] | Shin Y, Chang Y-C, Lee DSW, et al. Liquid Nuclear Condensates Mechanically Sense and Restructure the Genome. Cell. 2018; 175 (6): 1481-1491. e13. |
| [53] | Brangwynne Clifford P, Tompa P, Pappu Rohit V. Polymer physics of intracellular phase transitions. Nature Physics. 2015 2015/11/01; 11 (11): 899-904. |
| [54] | Shin Y, Brangwynne CP. Liquid phase condensation in cell physiology and disease. Science. 2017 Sep 22; 357 (6357). |
| [55] | Cho S, Irianto J, Discher DE. Mechanosensing by the nucleus: From pathways to scaling relationships. J Cell Biol. 2017 Feb; 216 (2): 305-315. |
| [56] | Sanulli S, Trnka MJ, Dharmarajan V, et al. HP1 reshapes nucleosome core to promote phase separation of heterochromatin. Nature. 2019 2019/11/01; 575 (7782): 390-394. |
| [57] | Monahan Z, Ryan VH, Janke AM, et al. Phosphorylation of the FUS low-complexity domain disrupts phase separation, aggregation, and toxicity. Embo J. 2017 Oct 16; 36 (20): 2951-2967. |
| [58] | Gardiner M, Toth R, Vandermoere F, et al. Identification and characterization of FUS/TLS as a new target of ATM. Biochem J. 2008 Oct 15; 415 (2): 297-307. |
| [59] | Deng Q, Holler CJ, Taylor G, et al. FUS is Phosphorylated by DNA-PK and Accumulates in the Cytoplasm after DNA Damage. The Journal of Neuroscience. 2014; 34 (23): 7802-7813. |
| [60] | Patel A, Malinovska L, Saha S, et al. ATP as a biological hydrotrope. Science. 2017; 356 (6339): 753-756. |
| [61] | Kang J, Lim L, Song J. ATP binds and inhibits the neurodegeneration-associated fibrillization of the FUS RRM domain. Commun Biol. 2019; 2: 223-223. |
| [62] | Du K, Arai S, Kawamura T, et al. TLS and PRMT1 synergistically coactivate transcription at the survivin promoter through TLS arginine methylation. Biochem Biophys Res Commun. 2011 Jan 28; 404 (4): 991-6. |
| [63] | Neumann M, Sampathu DM, Kwong LK, et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science. 2006 Oct 6; 314 (5796): 130-3. |
| [64] | Dormann D, Rodde R, Edbauer D, et al. ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import. Embo J. 2010 Aug 18; 29 (16): 2841-57. |
| [65] | Qamar S, Wang G, Randle SJ, et al. FUS Phase Separation Is Modulated by a Molecular Chaperone and Methylation of Arginine Cation-pi Interactions. Cell. 2018; 173 (3): 720-734. e15. |
| [66] | Long HK, Prescott SL, Wysocka J. Ever-Changing Landscapes: Transcriptional Enhancers in Development and Evolution. Cell. 2016 2016/11/17/; 167 (5): 1170-1187. |
| [67] | Whyte Warren A, Orlando David A, Hnisz D, et al. Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes. Cell. 2013 2013/04/11/; 153 (2): 307-319. |
| [68] | Nair SJ, Yang L, Meluzzi D, et al. Phase separation of ligand-activated enhancers licenses c ooperative chromosomal enhancer assembly. Nature Structural & Molecular Biology. 2019 2019/03/01; 26 (3): 193-203. |
| [69] | Hnisz D, Shrinivas K, Young RA, et al. A Phase Separation Model for Transcriptional Control. Cell. 2017; 169 (1): 13-23. |
| [70] | Brangwynne CP, Eckmann CR, Courson DS, et al. Germline P Granules Are Liquid Droplets That Localize by Controlled Dissolution/Condensation. Science. 2009; 324 (5935): 1729-1732. |
| [71] | Brangwynne CP, Mitchison TJ, Hyman AA. Active liquid-like behavior of nucleoli determines their size and shape in Xenopus laevis oocytes. Proceedings of the National Academy of Sciences. 2011; 108 (11): 4334-4339. |
| [72] | Banani SF, Lee HO, Hyman AA, et al. Biomolecular condensates: organizers of cellular biochemistry. Nature Reviews Molecular Cell Biology. 2017; 18: 285. |
| [73] | Chong S, Dugast-Darzacq C, Liu Z, et al. Imaging dynamic and selective low-complexity domain interactions that control gene transcription. Science. 2018; 361 (6400): eaar2555. |
| [74] | Lu H, Yu D, Hansen AS, et al. Phase-separation mechanism for C-terminal hyperphosphorylation of RNA polymerase II. Nature. 2018 2018/06/01; 558 (7709): 318-323. |
| [75] | Li W, Notani D, Ma Q, et al. Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation. Nature. 2013 Jun 27; 498 (7455): 516-20. |
| [76] | Liu Z, Merkurjev D, Yang F, et al. Enhancer Activation Requires trans-Recruitment of a Mega Transcription Factor Complex. Cell. 2014 2014/10/09/; 159 (2): 358-373. |
| [77] | Dyson HJ, Wright PE. Intrinsically unstructured proteins and their functions. Nature Reviews Molecular Cell Biology. 2005 2005/03/01; 6 (3): 197-208. |
| [78] | Lin Y, Mori E, Kato M, et al. Toxic PR Poly-Dipeptides Encoded by the C9orf72 Repeat Expansion Target LC Domain Polymers. Cell. 2016; 167 (3): 789-802. e12. |
| [79] | Aerts S, van Helden J, Sand O, et al. Fine-Tuning Enhancer Models to Predict Transcriptional Targets across Multiple Genomes. PloS one. 2007; 2: e1115. |
| [80] | McSwiggen DT, Mir M, Darzacq X, et al. Evaluating phase separation in live cells: diagnosis, caveats, and functional consequences. Genes & Development. 2019 October 8, 2019. |
| [81] | Alberti S, Gladfelter A, Mittag T. Considerations and Challenges in Studying Liquid-Liquid Phase Separation and Biomolecular Condensates. Cell. 2019 2019/01/24/; 176 (3): 419-434. |
| [82] | A P, Weber SC. Evidence for and against Liquid-Liquid Phase Separation in the Nucleus [Review]. Noncoding RNA. 2019 Nov 1; 5 (4). |
| [83] | Elbaum-Garfinkle S, Brangwynne CP. Liquids, Fibers, and Gels: The Many Phases of Neurodegeneration. Developmental cell. 2015 Dec 07; 35 (5): 531-2. |
| [84] | Minezaki Y, Homma K, Kinjo AR, et al. Human transcription factors contain a high fraction of intrinsically disordered regions essential for transcriptional regulation. J Mol Biol. 2006 Jun 16; 359 (4): 1137-49. |
| [85] | Nishikawa K. Natively unfolded proteins: An overview [Review]. Biophysics (Nagoya-shi). 2009; 5: 53-58. |
| [86] | Homma K, Anbo H, Noguchi T, et al. Both Intrinsically Disordered Regions and Structural Domains Evolve Rapidly in Immune-Related Mammalian Proteins. International Journal of Molecular Sciences. 2018; 19 (12): 3860. |
| [87] | Perez-Losada J, Sanchez-Martin M, Rodriguez-Garcia MA, et al. Liposarcoma initiated by FUS/TLS-CHOP: the FUS/TLS domain plays a critical role in the pathogenesis of liposarcoma. Oncogene. 2000 Dec 7; 19 (52): 6015-22. |
APA Style
Riki Kurokawa. (2020). Versatile Regulator or Integrator RNA-binding Protein TLS/FUS Works for Phase Separation on Regulation of the Human Genome - In Relation to Liposarcoma and ALS. Biomedical Sciences, 6(1), 5-16. https://doi.org/10.11648/j.bs.20200601.12
ACS Style
Riki Kurokawa. Versatile Regulator or Integrator RNA-binding Protein TLS/FUS Works for Phase Separation on Regulation of the Human Genome - In Relation to Liposarcoma and ALS. Biomed. Sci. 2020, 6(1), 5-16. doi: 10.11648/j.bs.20200601.12
AMA Style
Riki Kurokawa. Versatile Regulator or Integrator RNA-binding Protein TLS/FUS Works for Phase Separation on Regulation of the Human Genome - In Relation to Liposarcoma and ALS. Biomed Sci. 2020;6(1):5-16. doi: 10.11648/j.bs.20200601.12
Share This Article
Twitter
Linked In
Facebook
Copy
Download@article{10.11648/j.bs.20200601.12,
author = {Riki Kurokawa},
title = {Versatile Regulator or Integrator RNA-binding Protein TLS/FUS Works for Phase Separation on Regulation of the Human Genome - In Relation to Liposarcoma and ALS},
journal = {Biomedical Sciences},
volume = {6},
number = {1},
pages = {5-16},
doi = {10.11648/j.bs.20200601.12},
url = {https://doi.org/10.11648/j.bs.20200601.12},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.bs.20200601.12},
abstract = {This review article aims at comprehensive understanding of biological functions of RNA-binding proteins (RBPs) and cognate RNAs. For showing the divergent and dispersed aspects of RBP functions of the human genome in living cells, RBP TLS/FUS is chosen for these topics. Recent discovery of TLS as a phase transition or phase separation inducer presents previously unprecedented models regarding phase separation and enhancer functions in the genome. Trends in research altered up to interests or desire of scientists. Research activities of TLS/FUS have been dramatically drifted across over the last century. TLS was identified as a fusion gene product of TLS-CHOP of liposarcoma in 1993. Before announcement of the human genome draft, there were compelling desires to hunt novel genes. Gene cloning from libraries was one of prevalent activities at that time. Next wave came with describing TLS as a causative gene for familial amyotrophic lateral sclerosis (ALS). Investigation of lethal neurodegenerative disease, ALS has social impact. Elucidation of onset of ALS has progressed rapidly. Latest discovery with TLS is its solute for phase separation and phase transition into aggregation. The phase separation and resultant aggregation are pointed out in relation to the onset of ALS. Then, people rush to search for tide of TLS to phase separation in link to cause for ALS. Analysis of the phase separation could provide a novel outline for long distant regulation of gene in the genome. In this review article, the author focuses emerging trendy targets of a versatile molecule TLS and discuss scientific needs behind these orientation for a specific molecule in biological sciences.},
year = {2020}
}
TY - JOUR T1 - Versatile Regulator or Integrator RNA-binding Protein TLS/FUS Works for Phase Separation on Regulation of the Human Genome - In Relation to Liposarcoma and ALS AU - Riki Kurokawa Y1 - 2020/02/18 PY - 2020 N1 - https://doi.org/10.11648/j.bs.20200601.12 DO - 10.11648/j.bs.20200601.12 T2 - Biomedical Sciences JF - Biomedical Sciences JO - Biomedical Sciences SP - 5 EP - 16 PB - Science Publishing Group SN - 2575-3932 UR - https://doi.org/10.11648/j.bs.20200601.12 AB - This review article aims at comprehensive understanding of biological functions of RNA-binding proteins (RBPs) and cognate RNAs. For showing the divergent and dispersed aspects of RBP functions of the human genome in living cells, RBP TLS/FUS is chosen for these topics. Recent discovery of TLS as a phase transition or phase separation inducer presents previously unprecedented models regarding phase separation and enhancer functions in the genome. Trends in research altered up to interests or desire of scientists. Research activities of TLS/FUS have been dramatically drifted across over the last century. TLS was identified as a fusion gene product of TLS-CHOP of liposarcoma in 1993. Before announcement of the human genome draft, there were compelling desires to hunt novel genes. Gene cloning from libraries was one of prevalent activities at that time. Next wave came with describing TLS as a causative gene for familial amyotrophic lateral sclerosis (ALS). Investigation of lethal neurodegenerative disease, ALS has social impact. Elucidation of onset of ALS has progressed rapidly. Latest discovery with TLS is its solute for phase separation and phase transition into aggregation. The phase separation and resultant aggregation are pointed out in relation to the onset of ALS. Then, people rush to search for tide of TLS to phase separation in link to cause for ALS. Analysis of the phase separation could provide a novel outline for long distant regulation of gene in the genome. In this review article, the author focuses emerging trendy targets of a versatile molecule TLS and discuss scientific needs behind these orientation for a specific molecule in biological sciences. VL - 6 IS - 1 ER -
Information
Email: