Three-Dimensional Structure of RNA-Binding Protein TLS Co-Crystallized with Biotinylated Isoxazole
Biomedical Sciences
Volume 2, Issue 1, January 2016, Pages: 1-10
Received: Apr. 7, 2016; Accepted: Apr. 13, 2016; Published: Jun. 3, 2016
Views 2656      Downloads 136
Authors
Riki Kurokawa, Division of Gene Structure and Function, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan
Toshikazu Bando, Department of Chemistry, Graduate School of Science, Kyoto University, Kyoto, Japan
Article Tools
Follow on us
Abstract
RNA-binding protein TLS with specific mutations forms insoluble precipitates in motor neurons causing neuronal degenerative diseases like amyotrophic lateral sclerosis (ALS), and frontotemporal dementia. TLS at high concentration around 10 mg/ml is prone to be precipitated even without any mutation. The mutation on TLS is supposed to induce more precipitation than the wild type with uncovered molecular mechanism. Specific protein precipitation is one of major causes for the neuronal diseases like the Alzheimer disease with amyloid formations. Identification of a trigger of the precipitation formation is a key event at developing the therapeutics against these diseases. Screening candidate compounds from a chemical library to stimulate mouse embryonic stem cells into cardiomyocytes identified isoxazole, its relative compounds containing the COX-2 inhibitor and β lactamase-resistant antibiotics. Its derivative, biotinylated isoxazole (b-isox), was serendipitously found to be precipitated with divergent RNA-binding proteins through their low complexity domains. The b-isox precipitation of RNA-binding proteins should be a model system for formation of insoluble precipitates at neuronal degenerative diseases. We confirmed the precipitation of TLS with b-isox and analyzed the co-crystal formation. In silico analysis presents a model of crystallization of b-isox forming the β strand structure with wavy repetitive valleys. The valleys of the β sheet capture the unstructured LC domains of TLS and force them into also β strand shapes. This model sheds light on flexible feature of the LC domain that well fits the valleys of the b-isox crystals. This should be one major reason why various LC domains are involves in formation of insoluble precipitates, suggesting molecular mechanism for neurodegenerative disorders.
Keywords
TLS, FUS, Biotinylated Isoxazole, Low Complexity Domain, Amyotrophic Lateral Sclerosis
To cite this article
Riki Kurokawa, Toshikazu Bando, Three-Dimensional Structure of RNA-Binding Protein TLS Co-Crystallized with Biotinylated Isoxazole, Biomedical Sciences. Vol. 2, No. 1, 2016, pp. 1-10. doi: 10.11648/j.bs.20160201.11
Copyright
Copyright © 2016 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
References
[1]
Kurokawa R (Ed.). Long Noncoding RNAs: Springer; 2015.
[2]
Lipovich L, Tarca AL, Cai J, Jia H, Chugani HT, Sterner KN, Grossman LI, Uddin M, Hof PR, Sherwood CC, et al: Developmental changes in the transcriptome of human cerebral cortex tissue: long noncoding RNA transcripts. Cereb Cortex 2014, 24:1451-1459.
[3]
Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, Guernec G, Martin D, Merkel A, Knowles DG, et al: The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome research 2012, 22:1775-1789.
[4]
Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, Oyama R, Ravasi T, Lenhard B, Wells C, et al: The transcriptional landscape of the mammalian genome. Science 2005, 309:1559-1563.
[5]
Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, Thomas K, Presser A, Bernstein BE, van Oudenaarden A, et al: Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A 2009, 106:11667-11672.
[6]
Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, Tanzer A, Lagarde J, Lin W, Schlesinger F, et al: Landscape of transcription in human cells. Nature 2012, 489:101-108.
[7]
Necsulea A, Soumillon M, Warnefors M, Liechti A, Daish T, Zeller U, Baker JC, Grutzner F, Kaessmann H: The evolution of lncRNA repertoires and expression patterns in tetrapods. Nature 2014, 505:635-640.
[8]
Chi KR: Finding function in mystery transcripts. Nature 2016, 529:423-425.
[9]
Kurokawa R: Generation of Functional Long Noncoding RNA Through Transcription and Natural Selection. In Regulatory RNAs. Springer; 2012: 151-174
[10]
Kurokawa R: Long noncoding RNA as a regulator for transcription. Prog Mol Subcell Biol 2011, 51:29-41.
[11]
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.
[12]
Kurokawa R: Initiation of Transcription Generates Divergence of Long Noncoding RNAs. In Long Noncoding RNAs. Springer; 2015: 69-91
[13]
Kurokawa R, Rosenfeld MG, Glass CK: Transcriptional regulation through noncoding RNAs and epigenetic modifications. RNA Biol 2009, 6:233-236.
[14]
Carninci P, Sandelin A, Lenhard B, Katayama S, Shimokawa K, Ponjavic J, Semple CA, Taylor MS, Engstrom PG, Frith MC, et al: Genome-wide analysis of mammalian promoter architecture and evolution. Nat Genet 2006, 38:626-635.
[15]
Duret L, Chureau C, Samain S, Weissenbach J, Avner P: The Xist RNA gene evolved in eutherians by pseudogenization of a protein-coding gene. Science 2006, 312:1653-1655.
[16]
Johnsson P, Ackley A, Vidarsdottir L, Lui W-O, Corcoran M, Grandér D, Morris KV: A pseudogene long noncoding RNA network regulates PTEN transcription and translation in human cells. Nature structural & molecular biology 2013, 20:440-446.
[17]
Scarola M, Comisso E, Pascolo R, Chiaradia R, Maria Marion R, Schneider C, Blasco MA, Schoeftner S, Benetti R: Epigenetic silencing of Oct4 by a complex containing SUV39H1 and Oct4 pseudogene lncRNA. Nat Commun 2015, 6:7631.
[18]
Yoneda R, Suzuki S, Mashima T, Kondo K, Nagata T, Katahira M, Kurokawa R: 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.
[19]
Wang X, Arai S, Song X, Reichart D, Du K, Pascual G, Tempst P, Rosenfeld MG, Glass CK, Kurokawa R: Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription. Nature 2008, 454:126-130.
[20]
Kato M, Han TW, Xie S, Shi K, Du X, Wu LC, Mirzaei H, Goldsmith EJ, Longgood J, Pei J, et al: Cell-free formation of RNA granules: low complexity sequence domains form dynamic fibers within hydrogels. Cell 2012, 149:753-767.
[21]
Han TW, Kato M, Xie S, Wu LC, Mirzaei H, Pei J, Chen M, Xie Y, Allen J, Xiao G, McKnight SL: Cell-free formation of RNA granules: bound RNAs identify features and components of cellular assemblies. Cell 2012, 149:768-779.
[22]
Lagier-Tourenne C, Cleveland DW: Rethinking ALS: the FUS about TDP-43. Cell 2009, 136:1001-1004.
[23]
Kwiatkowski TJ, Jr., Bosco DA, Leclerc AL, Tamrazian E, Vanderburg CR, Russ C, Davis A, Gilchrist J, Kasarskis EJ, Munsat T, et al: Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 2009, 323:1205-1208.
[24]
Vance C, Rogelj B, Hortobagyi T, De Vos KJ, Nishimura AL, Sreedharan J, Hu X, Smith B, Ruddy D, Wright P, et al: Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 2009, 323:1208-1211.
[25]
Sun S, Ling S-C, Qiu J, Albuquerque CP, Zhou Y, Tokunaga S, Li H, Qiu H, Bui A, Yeo GW, et al: ALS-causative mutations in FUS/TLS confer gain and loss of function by altered association with SMN and U1-snRNP. Nat Commun 2015, 6.
[26]
Lagier-Tourenne C, Polymenidou M, Cleveland DW: TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration. Hum Mol Genet 2010, 19:R46-64.
[27]
Sadek H, Hannack B, Choe E, Wang J, Latif S, Garry MG, Garry DJ, Longgood J, Frantz DE, Olson EN, et al: Cardiogenic small molecules that enhance myocardial repair by stem cells. Proceedings of the National Academy of Sciences 2008, 105:6063-6068.
[28]
Song X, Wang X, Arai S, Kurokawa R: Promoter-associated noncoding RNA from the CCND1 promoter. Methods in molecular biology 2012, 809:609-622.
[29]
Guex N, Peitsch MC: SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis 1997, 18:2714-2723.
[30]
Rahman MM, Kitao S, Tsuji D, Suzuki K, Sakamoto J-I, Matsuoka K, Matsuzawa F, Aikawa S-I, Itoh K: Inhibitory effects and specificity of synthetic sialyldendrimers toward recombinant human cytosolic sialidase 2 (NEU2). Glycobiology 2013, 23:495-504.
[31]
King OD, Gitler AD, Shorter J: The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease. Brain Research 2012, 1462:61-80.
[32]
Alberti S, Halfmann R, King O, Kapila A, Lindquist S: A systematic survey identifies prions and illuminates sequence features of prionogenic proteins. Cell 2009, 137:146-158.
[33]
Livnah O, Bayer EA, Wilchek M, Sussman JL: Three-dimensional structures of avidin and the avidin-biotin complex. Proceedings of the National Academy of Sciences of the United States of America 1993, 90:5076-5080.
[34]
Kim HJ, Kim NC, Wang YD, Scarborough EA, Moore J, Diaz Z, MacLea KS, Freibaum B, Li S, Molliex A, et al: Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature 2013, 495:467-473.
[35]
Berchowitz Luke E, Kabachinski G, Walker Margaret R, Carlile Thomas M, Gilbert Wendy V, Schwartz Thomas U, Amon A: Regulated Formation of an Amyloid-like Translational Repressor Governs Gametogenesis. Cell 2015, 163:406-418.
[36]
Schwartz Jacob C, Wang X, Podell Elaine R, Cech Thomas R: RNA Seeds Higher-Order Assembly of FUS Protein. Cell Reports 2013, 5:918-925.
ADDRESS
Science Publishing Group
548 FASHION AVENUE
NEW YORK, NY 10018
U.S.A.
Tel: (001)347-688-8931