Jump to content

RNA-binding protein FUS

From Wikipedia, the free encyclopedia
(Redirected from FUS-CHOP)
FUS
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesFUS, ALS6, ETM4, FUS1, HNRNPP2, POMP75, TLS, FUS RNA binding protein, altFUS
External IDsOMIM: 137070; MGI: 1353633; GeneCards: FUS; OMA:FUS - orthologs
Orthologs
SpeciesHumanMouse
Entrez

2521

233908

Ensembl

ENSG00000089280

ENSMUSG00000030795

UniProt

P35637

P56959

RefSeq (mRNA)

NM_001010850
NM_001170634
NM_001170937
NM_004960

NM_139149
NM_001347649

RefSeq (protein)

NP_001164105
NP_001164408
NP_004951

NP_001334578
NP_631888

Location (UCSC)Chr 16: 31.18 – 31.19 MbChr 7: 127.57 – 127.58 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

RNA-binding protein fused in sarcoma/translocated in liposarcoma (FUS/TLS), also known as heterogeneous nuclear ribonucleoprotein P2 is a protein that in humans is encoded by the FUS gene.[5][6][7][8][9][10]

Discovery

[edit]

FUS/TLS was initially identified as a fusion protein (FUS-CHOP) produced as a result of chromosomal translocations in human cancers, especially liposarcomas.[6][9] In these instances, the promoter and N-terminal part of FUS/TLS is translocated to the C-terminal domain of various DNA-binding transcription factors (e.g. CHOP) conferring a strong transcriptional activation domain onto the fusion proteins.[11][12]

FUS/TLS was independently identified as the hnRNP P2 protein, a subunit of a complex involved in the maturation of pre-mRNA.[13]

Structure

[edit]

FUS/TLS is a member of the FET protein family that also includes the EWS protein, the TATA-binding protein TBP-associated factor TAFII68/TAF15, and the Drosophila cabeza/SARF protein.[14][11]

FUS/TLS, EWS and TAF15 have a similar structure, characterised by an N-terminal QGSY-rich region, a highly conserved RNA recognition motif (RRM), multiple RGG repeats, which are extensively demethylated at arginine residues[15] and a C-terminal zinc finger motif.[7][9][14][16]

Function

[edit]

The N-terminal end of FUS appears to be involved in transcriptional activation, while the C-terminal end is involved in protein and RNA binding. In addition recognition sites for the transcription factors AP2, GCF, Sp1 have been identified in FUS.[17]

Consistently, in vitro studies have shown that FUS/TLS binds RNA, single-stranded DNA and (with lower affinity) double-stranded DNA.[7][9][18][19][20][21] The sequence specificity of FUS/TLS binding to RNA or DNA has not been well established; however, using in vitro selection (SELEX), a common GGUG motif has been identified in approximately half of the RNA sequences bound by FUS/TLS.[22] A later proposal was that the GGUG motif is recognised by the zinc finger domain and not the RRM (80). Additionally, FUS/TLS has been found to bind a relatively long region in the 3′ untranslated region (UTR) of the actin-stabilising protein Nd1-L mRNA, suggesting that rather than recognising specific short sequences, FUS/TLS interacts with multiple RNA-binding motifs or recognises secondary conformations.[23] FUS/TLS has also been proposed to bind human telomeric RNA (UUAGGG)4 and single-stranded human telomeric DNA in vitro.[24]

Beyond nucleic acid binding, FUS/TLS was also found to associate with both general and more specialized protein factors to influence the initiation of transcription.[25] Indeed, FUS/TLS interacts with several nuclear receptors.[26] and with gene-specific transcription factors such as Spi-1/PU.1.[27] or NF-κB.[28] It also associates with the general transcriptional machinery and may influence transcription initiation and promoter selection by interacting with RNA polymerase II and the TFIID complex.[29][30][31] Recently, FUS/TLS was also shown to repress the transcription of RNAP III genes and to co-immunoprecipitate with TBP and the TFIIIB complex.[32]

FUS-mediated DNA repair

[edit]

FUS appears at sites of DNA damage very rapidly, which suggests that FUS is orchestrating the DNA repair response.[33] The function of FUS in the DNA damage response in neurons involves a direct interaction with histone deacetylase 1 (HDAC1). The recruitment of FUS to double-strand break sites is important for DNA damage response signaling and for repair of DNA damage.[33] FUS loss-of-function results in increased DNA damage in neurons. Mutations in the FUS nuclear localization sequence impairs the poly (ADP-ribose) polymerase (PARP)-dependent DNA damage response.[34] This impairment leads to neurodegeneration and FUS aggregate formation. Such FUS aggregates are a pathological hallmark of the neurodegenerative disease amyotrophic lateral sclerosis (ALS).

Clinical significance

[edit]

FUS gene rearrangement has been implicated in the pathogenesis of myxoid liposarcoma, low-grade fibromyxoid sarcoma, Ewing sarcoma, and a wide range of other malignant and benign tumors (see FET protein family).[35]

In 2009 two separate research groups analysed 26 unrelated families who presented with a type6 ALS phenotype, and found 14 mutations in the FUS gene.[36][37]

Subsequently, FUS has also emerged as a significant disease protein in a subgroup of frontotemporal dementias (FTDs), previously characterized by immunoreactivity of the inclusion bodies for ubiquitin, but not for TDP-43 or tau with a proportion of the inclusions also containing alpha-internexin (α-internexin) in a further subgroup known as neuronal intermediate filament inclusion disease (NIFID). The disease entities which are now considered subtypes of FTLD-FUS are atypical frontotemporal lobar degeneration with ubiquitinated inclusions (aFTLD-U), NIFID, and basophilic inclusion body disease (BIBD), which together with ALS-FUS comprise the FUS-proteopathies.[38][39][40][41]

Frontotemporal lobar degeneration (FTLD) is the pathological term for the clinical syndrome of frontotemporal dementia (FTD). FTD differs from the more common Alzheimer's dementia in that memory is relatively well preserved; instead, the disease presents with a more temporal-lobe phenotype. Behavioral variant frontotemporal dementia (bvFTD), progressive non-fluent aphasia (PNFA) and semantic dementia (SD) are the three best-characterised clinical presentations. FUS positive FTLD tends to present clinically as a bvFTD but the correlation between underlying pathology and clinical presentation is not perfect.

Toxic mechanism in ALS

[edit]

The toxic mechanism by which mutant FUS causes ALS is currently unclear. It is known that many of the ALS-linked mutations are located in its C-terminal nuclear localisation signal, resulting in it being located in the cytoplasm rather than the nucleus (where wild-type FUS primarily resides).[42] This suggests either a loss of nuclear function, or a toxic gain of cytoplasmic function, is responsible for the development of this type of ALS. Many researchers believe the toxic gain of cytoplasmic function model to be more likely as mouse models that do not express FUS, and therefore have a complete loss of nuclear FUS function, do not develop clear ALS-like symptoms.[43]

Interactions

[edit]

FUS has been shown to interact with:

References

[edit]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000089280 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030795 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Eneroth M, Mandahl N, Heim S, Willén H, Rydholm A, Alberts KA, Mitelman F (Aug 1990). "Localization of the chromosomal breakpoints of the t(12;16) in liposarcoma to subbands 12q13.3 and 16p11.2". Cancer Genet Cytogenet. 48 (1): 101–7. doi:10.1016/0165-4608(90)90222-V. PMID 2372777.
  6. ^ a b Rabbitts TH, Forster A, Larson R, Nathan P (Sep 1993). "Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma". Nat Genet. 4 (2): 175–80. doi:10.1038/ng0693-175. PMID 7503811. S2CID 5964293.
  7. ^ a b c Prasad DD, Ouchida M, Lee L, Rao VN, Reddy ES (December 1994). "TLS/FUS fusion domain of TLS/FUS-erg chimeric protein resulting from the t(16;21) chromosomal translocation in human myeloid leukemia functions as a transcriptional activation domain". Oncogene. 9 (12): 3717–29. PMID 7970732.
  8. ^ "Entrez Gene: FUS fusion (involved in t(12;16) in malignant liposarcoma)".
  9. ^ a b c d Crozat A, Aman P, Mandahl N, Ron D (June 1993). "Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma". Nature. 363 (6430): 640–4. Bibcode:1993Natur.363..640C. doi:10.1038/363640a0. PMID 8510758. S2CID 4358184.
  10. ^ Mrózek K, Karakousis CP, Bloomfield CD (April 1993). "Chromosome 12 breakpoints are cytogenetically different in benign and malignant lipogenic tumors: localization of breakpoints in lipoma to 12q15 and in myxoid liposarcoma to 12q13.3". Cancer Res. 53 (7): 1670–5. PMID 8453640.
  11. ^ a b Bertolotti A, Bell B, Tora L (December 1999). "The N-terminal domain of human TAFII68 displays transactivation and oncogenic properties". Oncogene. 18 (56): 8000–10. doi:10.1038/sj.onc.1203207. PMID 10637511.
  12. ^ Zinszner H, Albalat R, Ron D (November 1994). "A novel effector domain from the RNA-binding protein TLS or EWS is required for oncogenic transformation by CHOP". Genes Dev. 8 (21): 2513–26. doi:10.1101/gad.8.21.2513. PMID 7958914.
  13. ^ Calvio C, Neubauer G, Mann M, Lamond AI (September 1995). "Identification of hnRNP P2 as TLS/FUS using electrospray mass spectrometry". RNA. 1 (7): 724–33. PMC 1369314. PMID 7585257.
  14. ^ a b Morohoshi F, Ootsuka Y, Arai K, Ichikawa H, Mitani S, Munakata N, Ohki M (October 1998). "Genomic structure of the human RBP56/hTAFII68 and FUS/TLS genes". Gene. 221 (2): 191–8. doi:10.1016/S0378-1119(98)00463-6. PMID 9795213.
  15. ^ Rappsilber J, Friesen WJ, Paushkin S, Dreyfuss G, Mann M (July 2003). "Detection of arginine dimethylated peptides by parallel precursor ion scanning mass spectrometry in positive ion mode". Anal. Chem. 75 (13): 3107–14. doi:10.1021/ac026283q. PMID 12964758.
  16. ^ Iko Y, Kodama TS, Kasai N, Oyama T, Morita EH, Muto T, Okumura M, Fujii R, Takumi T, Tate S, Morikawa K (October 2004). "Domain architectures and characterization of an RNA-binding protein, TLS". J. Biol. Chem. 279 (43): 44834–40. doi:10.1074/jbc.M408552200. PMID 15299008.
  17. ^ Aman P, Panagopoulos I, Lassen C, Fioretos T, Mencinger M, Toresson H, Höglund M, Forster A, Rabbitts TH, Ron D, Mandahl N, Mitelman F (October 1996). "Expression patterns of the human sarcoma-associated genes FUS and EWS and the genomic structure of FUS". Genomics. 37 (1): 1–8. doi:10.1006/geno.1996.0513. PMID 8921363.
  18. ^ Zinszner H, Sok J, Immanuel D, Yin Y, Ron D (August 1997). "TLS (FUS) binds RNA in vivo and engages in nucleo-cytoplasmic shuttling". J. Cell Sci. 110 (15): 1741–50. doi:10.1242/jcs.110.15.1741. PMID 9264461.
  19. ^ Perrotti D, Bonatti S, Trotta R, Martinez R, Skorski T, Salomoni P, Grassilli E, Lozzo RV, Cooper DR, Calabretta B (August 1998). "TLS/FUS, a pro-oncogene involved in multiple chromosomal translocations, is a novel regulator of BCR/ABL-mediated leukemogenesis". EMBO J. 17 (15): 4442–55. doi:10.1093/emboj/17.15.4442. PMC 1170776. PMID 9687511.
  20. ^ Baechtold H, Kuroda M, Sok J, Ron D, Lopez BS, Akhmedov AT (November 1999). "Human 75-kDa DNA-pairing protein is identical to the pro-oncoprotein TLS/FUS and is able to promote D-loop formation". J. Biol. Chem. 274 (48): 34337–42. doi:10.1074/jbc.274.48.34337. PMID 10567410.
  21. ^ Wang X, Arai S, Song X, Reichart D, Du K, Pascual G, Tempst P, Rosenfeld MG, Glass CK, Kurokawa R (July 2008). "Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription". Nature. 454 (7200): 126–30. Bibcode:2008Natur.454..126W. doi:10.1038/nature06992. PMC 2823488. PMID 18509338.
  22. ^ Lerga A, Hallier M, Delva L, Orvain C, Gallais I, Marie J, Moreau-Gachelin F (March 2001). "Identification of an RNA binding specificity for the potential splicing factor TLS". J. Biol. Chem. 276 (9): 6807–16. doi:10.1074/jbc.M008304200. PMID 11098054.
  23. ^ Fujii R, Takumi T (December 2005). "TLS facilitates transport of mRNA encoding an actin-stabilizing protein to dendritic spines". J. Cell Sci. 118 (Pt 24): 5755–65. doi:10.1242/jcs.02692. PMID 16317045.
  24. ^ Takahama K, Kino K, Arai S, Kurokawa R, Oyoshi T (2008). "Identification of RNA binding specificity for the TET-family proteins". Nucleic Acids Symp Ser (Oxf). 52 (52): 213–4. doi:10.1093/nass/nrn108. PMID 18776329.
  25. ^ Law WJ, Cann KL, Hicks GG (March 2006). "TLS, EWS and TAF15: a model for transcriptional integration of gene expression". Brief Funct Genomic Proteomic. 5 (1): 8–14. doi:10.1093/bfgp/ell015. PMID 16769671.
  26. ^ Powers CA, Mathur M, Raaka BM, Ron D, Samuels HH (January 1998). "TLS (translocated-in-liposarcoma) is a high-affinity interactor for steroid, thyroid hormone, and retinoid receptors". Mol. Endocrinol. 12 (1): 4–18. doi:10.1210/mend.12.1.0043. PMID 9440806.
  27. ^ a b Hallier M, Lerga A, Barnache S, Tavitian A, Moreau-Gachelin F (February 1998). "The transcription factor Spi-1/PU.1 interacts with the potential splicing factor TLS". J. Biol. Chem. 273 (9): 4838–42. doi:10.1074/jbc.273.9.4838. PMID 9478924.
  28. ^ a b Uranishi H, Tetsuka T, Yamashita M, Asamitsu K, Shimizu M, Itoh M, Okamoto T (April 2001). "Involvement of the pro-oncoprotein TLS (translocated in liposarcoma) in nuclear factor-kappa B p65-mediated transcription as a coactivator". J. Biol. Chem. 276 (16): 13395–401. doi:10.1074/jbc.M011176200. PMID 11278855.
  29. ^ Bertolotti A, Lutz Y, Heard DJ, Chambon P, Tora L (September 1996). "hTAF(II)68, a novel RNA/ssDNA-binding protein with homology to the pro-oncoproteins TLS/FUS and EWS is associated with both TFIID and RNA polymerase II". EMBO J. 15 (18): 5022–31. doi:10.1002/j.1460-2075.1996.tb00882.x. PMC 452240. PMID 8890175.
  30. ^ Bertolotti A, Melot T, Acker J, Vigneron M, Delattre O, Tora L (March 1998). "EWS, but not EWS-FLI-1, is associated with both TFIID and RNA polymerase II: interactions between two members of the TET family, EWS and hTAFII68, and subunits of TFIID and RNA polymerase II complexes". Mol. Cell. Biol. 18 (3): 1489–97. doi:10.1128/mcb.18.3.1489. PMC 108863. PMID 9488465.
  31. ^ a b Yang L, Embree LJ, Hickstein DD (May 2000). "TLS-ERG leukemia fusion protein inhibits RNA splicing mediated by serine-arginine proteins". Mol. Cell. Biol. 20 (10): 3345–54. doi:10.1128/MCB.20.10.3345-3354.2000. PMC 85627. PMID 10779324.
  32. ^ Tan AY, Manley JL (January 2010). "TLS inhibits RNA polymerase III transcription". Mol. Cell. Biol. 30 (1): 186–96. doi:10.1128/MCB.00884-09. PMC 2798296. PMID 19841068.
  33. ^ a b c Wang WY, Pan L, Su SC, Quinn EJ, Sasaki M, Jimenez JC, Mackenzie IR, Huang EJ, Tsai LH (October 2013). "Interaction of FUS and HDAC1 regulates DNA damage response and repair in neurons". Nature Neuroscience. 16 (10): 1383–91. doi:10.1038/nn.3514. PMC 5564396. PMID 24036913.
  34. ^ Naumann M, Pal A, Goswami A, Lojewski X, Japtok J, Vehlow A, Naujock M, Günther R, Jin M, Stanslowsky N, Reinhardt P, Sterneckert J, Frickenhaus M, Pan-Montojo F, Storkebaum E, Poser I, Freischmidt A, Weishaupt JH, Holzmann K, Troost D, Ludolph AC, Boeckers TM, Liebau S, Petri S, Cordes N, Hyman AA, Wegner F, Grill SW, Weis J, Storch A, Hermann A (January 2018). "Impaired DNA damage response signaling by FUS-NLS mutations leads to neurodegeneration and FUS aggregate formation". Nat Commun. 9 (1): 335. Bibcode:2018NatCo...9..335N. doi:10.1038/s41467-017-02299-1. PMC 5780468. PMID 29362359.
  35. ^ Flucke U, van Noesel MM, Siozopoulou V, Creytens D, Tops BB, van Gorp JM, Hiemcke-Jiwa LS (June 2021). "EWSR1-The Most Common Rearranged Gene in Soft Tissue Lesions, Which Also Occurs in Different Bone Lesions: An Updated Review". Diagnostics (Basel, Switzerland). 11 (6): 1093. doi:10.3390/diagnostics11061093. PMC 8232650. PMID 34203801.
  36. ^ Kwiatkowski TJ, Bosco DA, Leclerc AL, Tamrazian E, Vanderburg CR, Russ C, Davis A, Gilchrist J, Kasarskis EJ, Munsat T, Valdmanis P, Rouleau GA, Hosler BA, Cortelli P, de Jong PJ, Yoshinaga Y, Haines JL, Pericak-Vance MA, Yan J, Ticozzi N, Siddique T, McKenna-Yasek D, Sapp PC, Horvitz HR, Landers JE, Brown RH (February 2009). "Mutations in the FUS/TLS Gene on Chromosome 16 Cause Familial Amyotrophic Lateral Sclerosis". Science. 323 (5918): 1205–1208. Bibcode:2009Sci...323.1205K. doi:10.1126/science.1166066. PMID 19251627. S2CID 12774563.
  37. ^ Vance C, Rogelj B, Hortobágyi T, De Vos KJ, Nishimura AL, Sreedharan J, Hu X, Smith B, Ruddy D, Wright P, Ganesalingam J, Williams KL, Tripathi V, Al-Saraj S, Al-Chalabi A, Leigh PN, Blair IP, Nicholson G, de Belleroche J, Gallo JM, Miller CC, Shaw CE (February 2009). "Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6". Science. 323 (5918): 1208–11. Bibcode:2009Sci...323.1208V. doi:10.1126/science.1165942. PMC 4516382. PMID 19251628.
  38. ^ Mackenzie IR, Rademakers R, Neumann M (October 2010). "TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia". Lancet Neurol. 9 (10): 995–1007. doi:10.1016/S1474-4422(10)70195-2. PMID 20864052. S2CID 5754428.
  39. ^ Munoz DG, Neumann M, Kusaka H, Yokota O, Ishihara K, Terada S, Kuroda S, Mackenzie IR (November 2009). "FUS pathology in basophilic inclusion body disease". Acta Neuropathol. 118 (5): 617–27. doi:10.1007/s00401-009-0598-9. hdl:2429/54671. PMID 19830439. S2CID 22541167.
  40. ^ Neumann M, Rademakers R, Roeber S, Baker M, Kretzschmar HA, Mackenzie IR (November 2009). "A new subtype of frontotemporal lobar degeneration with FUS pathology". Brain. 132 (Pt 11): 2922–31. doi:10.1093/brain/awp214. PMC 2768659. PMID 19674978.
  41. ^ Neumann M, Roeber S, Kretzschmar HA, Rademakers R, Baker M, Mackenzie IR (November 2009). "Abundant FUS-immunoreactive pathology in neuronal intermediate filament inclusion disease". Acta Neuropathol. 118 (5): 605–16. doi:10.1007/s00401-009-0581-5. PMC 2864784. PMID 19669651.
  42. ^ "FUS - RNA-binding protein FUS - Homo sapiens (Human) - FUS gene & protein". www.uniprot.org. Retrieved 2019-03-13.
  43. ^ Kino Y, Washizu C, Kurosawa M, Yamada M, Miyazaki H, Akagi T, Hashikawa T, Doi H, Takumi T, Hicks GG, Hattori N, Shimogori T, Nukina N (April 2015). "FUS/TLS deficiency causes behavioral and pathological abnormalities distinct from amyotrophic lateral sclerosis". Acta Neuropathologica Communications. 3: 24. doi:10.1186/s40478-015-0202-6. PMC 4408580. PMID 25907258.
  44. ^ Saunders LR, Perkins DJ, Balachandran S, Michaels R, Ford R, Mayeda A, Barber GN (August 2001). "Characterization of two evolutionarily conserved, alternatively spliced nuclear phosphoproteins, NFAR-1 and -2, that function in mRNA processing and interact with the double-stranded RNA-dependent protein kinase, PKR". J. Biol. Chem. 276 (34): 32300–12. doi:10.1074/jbc.M104207200. PMID 11438536.
  45. ^ Wada K, Inoue K, Hagiwara M (August 2002). "Identification of methylated proteins by protein arginine N-methyltransferase 1, PRMT1, with a new expression cloning strategy". Biochim. Biophys. Acta. 1591 (1–3): 1–10. doi:10.1016/S0167-4889(02)00202-1. PMID 12183049.
  46. ^ Lee J, Bedford MT (March 2002). "PABP1 identified as an arginine methyltransferase substrate using high-density protein arrays". EMBO Rep. 3 (3): 268–73. doi:10.1093/embo-reports/kvf052. PMC 1084016. PMID 11850402.
  47. ^ Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE (September 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. hdl:11858/00-001M-0000-0010-8592-0. PMID 16169070. S2CID 8235923.
  48. ^ Burke KA, Janke AM, Rhine CL, Fawzi NL (October 15, 2015). "Residue-by-Residue View of In Vitro FUS Granules that Bind the C-Terminal Domain of RNA Polymerase II". Mol. Cell. 60 (2): 231–241. doi:10.1016/j.molcel.2015.09.006. PMC 4609301. PMID 26455390.
  49. ^ Dormann D, Rodde R, Edbauer D, Bentmann E, Fischer I, Hruscha A, Than ME, Mackenzie IR, Capell A, Schmid B, Neumann M, Haass C (August 2010). "ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import". EMBO J. 29 (16): 2841–57. doi:10.1038/emboj.2010.143. PMC 2924641. PMID 20606625.
  50. ^ Brelstaff J, Lashley T, Holton JL, Lees AJ, Rossor MN, Bandopadhyay R, Revesz T (November 2011). "Transportin1: a marker of FTLD-FUS". Acta Neuropathol. 122 (5): 591–600. doi:10.1007/s00401-011-0863-6. PMID 21847626. S2CID 5913873.

Further reading

[edit]
Retrieved from "https://en.wikipedia.org/w/index.php?title=RNA-binding_protein_FUS&oldid=1247346793"