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Original Article

Early lethality and neuronal proteinopathy in mice expressing cytoplasm-targeted FUS that lacks the RNA recognition motif

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Pages 402-409 | Received 28 Dec 2014, Accepted 08 Mar 2015, Published online: 20 May 2015

References

  • Ling SC, Polymenidou M, Cleveland DW. Converging mechanisms in ALS and FTD: disrupted RNA and protein homeostasis. Neuron. 2013;79:416–38.
  • Kwiatkowski TJ Jr, Bosco DA, Leclerc AL, Tamrazian E, Vanderburg CR, Russ C, et al. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science. 2009;323:1205–8.
  • Vance C, Rogelj B, Hortobagyi T, de Vos KJ, Nishimura AL, Sreedharan J, et al. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science. 2009;323:1208–11.
  • Hewitt C, Kirby J, Highley JR, Hartley JA, Hibberd R, Hollinger HC, et al. Novel FUS/TLS mutations and pathology in familial and sporadic amyotrophic lateral sclerosis. Arch Neurol. 2010;67:455–61.
  • Munoz DG, Neumann M, Kusaka H, Yokota O, Ishihara K, Terada S, et al. FUS pathology in basophilic inclusion body disease. Acta Neuropathol. 2009;118:617–27.
  • Neumann M, Roeber S, Kretzschmar HA, Rademakers R, Baker M, Mackenzie IR. Abundant FUS-immunoreactive pathology in neuronal intermediate filament inclusion disease. Acta Neuropathol. 2009;118:605–16.
  • Doi H, Koyano S, Suzuki Y, Nukina N, Kuroiwa Y. The RNA binding protein FUS/TLS is a common aggregate-interacting protein in polyglutamine diseases. Neurosci Res. 2010; 66:131–3.
  • Doi H, Okamura K, Bauer PO, Furukawa Y, Shimizu H, Kurosawa M, et al. RNA binding protein TLS is a major nuclear aggregate-interacting protein in Huntingtin exon 1 with expanded polyglutamine-expressing cells. J Biol Chem. 2008;283:6489–500.
  • Iko Y, Kodama TS, Kasai N, Oyama T, Morita EH, Muto T, et al. Domain architectures and characterization of an RNA binding protein, TLS. J Biol Chem. 2004;279:44834–40.
  • Lerga A, Hallier M, Delva L, Orvain C, Gallais I, Marie J, et al. Identification of an RNA binding specificity for the potential splicing factor TLS. J Biol Chem. 2001;276:6807–16.
  • Tan AY, Manley JL. TLS inhibits RNA polymerase III transcription. Mol Cell Biol. 2010;30:186–96.
  • Tan AY, Riley TR, Coady T, Bussemaker HJ, Manley JL. TLS/FUS (translocated in liposarcoma/fused in sarcoma) regulates target gene transcription via single-stranded DNA response elements. Proc Natl Acad Sci U S A. 2012; 109:6030–5.
  • Wang X, Arai S, Song X, Reichart D, Du K, Pascual G, et al. Induced ncRNAs allosterically modify RNA binding proteins in cis to inhibit transcription. Nature. 2008;454: 126–30.
  • Schwartz JC, Ebmeier CC, Podell ER, Heimiller J, Taatjes DJ, Cech TR. FUS binds the CTD of RNA polymerase II and regulates its phosphorylation at Ser2. Genes Dev. 2012; 26:2690–5.
  • Ishigaki S, Masuda A, Fujioka Y, Iguchi Y, Katsuno M, Shibata A, et al. Position-dependent FUS-RNA interactions regulate alternative splicing events and transcriptions. Sci Rep. 2012;2:529.
  • Nakaya T, Alexiou P, Maragkakis M, Chang A, Mourelatos Z. FUS regulates genes coding for RNA binding proteins in neurons by binding to their highly conserved introns. RNA. 2013;19:498–509.
  • Orozco D, Tahirovic S, Rentzsch K, Schwenk BM, Haass C, Edbauer D. Loss of fused in sarcoma (FUS) promotes pathological tau splicing. EMBO Rep. 2012;13:759–64.
  • Zhou Y, Liu S, Liu G, Ozturk A, Hicks GG. ALS associated FUS mutations result in compromised FUS alternative splicing and autoregulation. PLoS Genet. 2013;9:e1003895.
  • Zinszner H, Sok J, Immanuel D, Yin Y, Ron D. TLS (FUS) binds RNA in vivo and engages in nucleo-cytoplasmic shuttling. J Cell Sci. 1997;110:1741–50.
  • Fujii R, Takumi T. TLS facilitates transport of mRNA encoding an actin-stabilizing protein to dendritic spines. J Cell Sci. 2005;118:5755–65.
  • Kanai Y, Dohmae N, Hirokawa N. Kinesin transports RNA: isolation and characterization of an RNA-transporting granule. Neuron. 2004;43:513–25.
  • Dormann D, Rodde R, Edbauer D, Bentmann E, Fischer I, Hruscha A, et al. ALS associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import. EMBO J. 2010;29:2841–57.
  • Dormann D, Madl T, Valori CF, Bentmann E, Tahirovic S, Abou-Ajram C, et al. Arginine methylation next to the PY-NLS modulates Transportin binding and nuclear import of FUS. EMBO J. 2012;31:4258–75.
  • Deng Q, Holler CJ, Taylor G, Hudson KF, Watkins W, Gearing M, et al. FUS is Phosphorylated by DNA-PK and Accumulates in the Cytoplasm after DNA Damage. J Neurosci. 2014;34:7802–13.
  • Shelkovnikova TA, Robinson HK, Southcombe JA, Ninkina N, Buchman VL. Multistep process of FUS aggregation in the cell cytoplasm involves RNA-dependent and RNA-independent mechanisms. Hum Mol Genet. 2014; 23:5211–26.
  • Anderson P, Kedersha N. Stress granules: the Tao of RNA triage. Trends Biochem Sci. 2008;33:141–50.
  • Shelkovnikova TA, Robinson H, Connor-Robson N, Buchman VL. Recruitment into stress granules prevents irreversible aggregation of FUS protein mislocalized to the cytoplasm. Cell Cycle. 2013;12:3194–202.
  • Shelkovnikova TA, Peters OM, Deykin AV, Connor-Robson N, Robinson H, Ustyugov AA, et al. Fused in Sarcoma (FUS) Protein Lacking Nuclear Localization Signal (NLS) and Major RNA Binding Motifs Triggers Proteinopathy and Severe Motor Phenotype in Transgenic Mice. J Biol Chem. 2013;288:25266–74.
  • Lagier-Tourenne C, Polymenidou M, Hutt KR, Vu AQ, Baughn M, Huelga SC, et al. Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs. Nat Neurosci. 2012;15:1488–97.
  • Bentmann E, Neumann M, Tahirovic S, Rodde R, Dormann D, Haass C. Requirements for stress granule recruitment of fused in sarcoma (FUS) and TAR DNA-binding protein of 43 kDa (TDP-43). J Biol Chem. 2012;287:23079–92304.
  • Liu X, Niu C, Ren J, Zhang J, Xie X, Zhu H, et al. The RRM domain of human fused in sarcoma protein reveals a non-canonical nucleic acid binding site. Biochim Biophys Acta. 2013;1832:375–85.
  • Clery A, Blatter M, Allain FH. RNA recognition motifs: boring? Not quite. Curr Opin Struct Biol. 2008;18:290–8.
  • Liu X, Niu C, Ren J, Zhang J, Xie X, Zhu H, et al. The RRM domain of human fused in sarcoma protein reveals a non-canonical nucleic acid binding site. Biochim Biophys Acta. 2012;1832:375–85.
  • Luthi A, van der Putten H, Botteri FM, Mansuy IM, Meins M, Frey U, et al. Endogenous serine protease inhibitor modulates epileptic activity and hippocampal long-term potentiation. J Neurosci. 1997;17:4688–99.
  • Ninkina N, Peters O, Millership S, Salem H, van der Putten H, Buchman VL. Gamma-synucleinopathy: neurodegeneration associated with overexpression of the mouse protein. Hum Mol Gen. 2009;18:1779–94.
  • Peters OM, Millership S, Shelkovnikova TA, Soto I, Keeling L, Hann A, et al. Selective pattern of motor system damage in gamma-synuclein transgenic mice mirrors the respective pathology in amyotrophic lateral sclerosis. Neurobiol Dis. 2012;48:124–31.
  • Shelkovnikova TA, Robinson HK, Troakes C, Ninkina N, Buchman VL. Compromised paraspeckle formation as a pathogenic factor in FUSopathies. Hum Mol Gen. 2014;23:2298–312.
  • Schmittgen TD, Livak KJ. Analysing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3:1101–8.
  • Blair IP, Williams KL, Warraich ST, Durnall JC, Thoeng AD, Manavis J, et al. FUS mutations in amyotrophic lateral sclerosis: clinical, pathological, neurophysiological and genetic analysis. J Neurol Neurosurg Psychiatry. 2010;81:639–45.
  • DePaul R, Abbs JH, Caligiuri M, Gracco VL, Brooks BR. Hypoglossal, trigeminal, and facial motor neuron involvement in amyotrophic lateral sclerosis. Neurology. 1988;38:281–3.
  • Huang C, Zhou H, Tong J, Chen H, Liu YJ, Wang D, et al. FUS transgenic rats develop the phenotypes of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. PLoS Genet. 2011;7:e1002011.
  • Qiu H, Lee S, Shang Y, Wang WY, Au KF, Kamiya S, et al. ALS associated mutation FUS-R521C causes DNA damage and RNA splicing defects. J Clin Invest. 2014;124:981–99.
  • Shelkovnikova TA. Modelling FUSopathies: focus on protein aggregation. Biochem Soc Trans. 2013;41:1613–7.
  • Colombrita C, Onesto E, Megiorni F, Pizzuti A, Baralle FE, Buratti E, et al. TDP-43 and FUS RNA-binding proteins bind distinct sets of cytoplasmic messenger RNAs and differently regulate their post-transcriptional fate in motor neuron-like cells. J Biol Chem. 2012;287:15635–47.
  • Mitchell JC, McGoldrick P, Vance C, Hortobagyi T, Sreedharan J, Rogelj B, et al. Overexpression of human wild-type FUS causes progressive motor neuron degeneration in an age- and dose-dependent fashion. Acta Neuropathol. 2013;125:273–88.

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