{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:46:16Z","timestamp":1791279976609,"version":"4.1.0"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2013,1,25]],"date-time":"2013-01-25T00:00:00Z","timestamp":1359072000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"},{"start":{"date-parts":[[2013,1,25]],"date-time":"2013-01-25T00:00:00Z","timestamp":1359072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO Mol Med"],"published-print":{"date-parts":[[2013,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Two motor neuron diseases, amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), are caused by distinct genes involved in RNA metabolism, TDP\u201043 and FUS\/TLS, and SMN, respectively. However, whether there is a shared defective mechanism in RNA metabolism common to these two diseases remains unclear. Here, we show that TDP\u201043 and FUS\/TLS localize in nuclear Gems through an association with SMN, and that all three proteins function in spliceosome maintenance. We also show that in ALS, Gems are lost, U snRNA levels are up\u2010regulated and spliceosomal U snRNPs abnormally and extensively accumulate in motor neuron nuclei, but not in the temporal lobe of FTLD with TDP\u201043 pathology. This aberrant accumulation of U snRNAs in ALS motor neurons is in direct contrast to SMA motor neurons, which show reduced amounts of U snRNAs, while both have defects in the spliceosome. These findings indicate that a profound loss of spliceosome integrity is a critical mechanism common to neurodegeneration in ALS and SMA, and may explain cell\u2010type specific vulnerability of motor neurons.<\/jats:p>","DOI":"10.1002\/emmm.201202303","type":"journal-article","created":{"date-parts":[[2012,12,19]],"date-time":"2012-12-19T02:49:11Z","timestamp":1355885351000},"page":"221-234","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":200,"title":["Spliceosome integrity is defective in the motor neuron diseases ALS and SMA"],"prefix":"10.1038","volume":"5","author":[{"given":"Hitomi","family":"Tsuiji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Iguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asako","family":"Furuya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayane","family":"Kataoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Hatsuta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Atsuta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiaki","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Hashizume","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyasu","family":"Akatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeo","family":"Murayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gen","family":"Sobue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Yamanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,1,25]]},"reference":[{"key":"BFEMMM201202303_CR1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nrneurol.2011.150","volume":"7","author":"PM Andersen","year":"2011","unstructured":"Andersen PM, Al\u2010Chalabi A (2011) Clinical genetics of amyotrophic lateral sclerosis: what do we really know? Nat Rev Neurol 7: 603\u2010615","journal-title":"Nat Rev Neurol"},{"key":"BFEMMM201202303_CR2","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.bbrc.2006.10.093","volume":"351","author":"T Arai","year":"2006","unstructured":"Arai T, Hasegawa M, Akiyama H, Ikeda K, Nonaka T, Mori H, Mann D, Tsuchiya K, Yoshida M, Hashizume Y, et al (2006) TDP\u201043 is a component of ubiquitin\u2010positive tau\u2010negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun 351: 602\u2010611","journal-title":"Biochem Biophys Res Commun"},{"key":"BFEMMM201202303_CR3","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/emboj.2010.310","volume":"30","author":"YM Ayala","year":"2011","unstructured":"Ayala YM, De Conti L, Avendano\u2010Vazquez SE, Dhir A, Romano M, D'Ambrogio A, Tollervey J, Ule J, Baralle M, Buratti E, et al (2011) TDP\u201043 regulates its mRNA levels through a negative feedback loop. EMBO J 30: 277\u2010288","journal-title":"EMBO J"},{"key":"BFEMMM201202303_CR4","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.cell.2012.05.029","volume":"150","author":"MG Berg","year":"2012","unstructured":"Berg MG, Singh LN, Younis I, Liu Q, Pinto AM, Kaida D, Zhang Z, Cho S, Sherrill\u2010Mix S, Wan L et al (2012) U1 snRNP determines mRNA length and regulates isoform expression. Cell 150: 53\u201064","journal-title":"Cell"},{"key":"BFEMMM201202303_CR5","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1212\/WNL.0b013e318249f697","volume":"78","author":"HM Blauw","year":"2012","unstructured":"Blauw HM, Barnes CP, van Vught PW, van Rheenen W, Verheul M, Cuppen E, Veldink JH, van den Berg LH (2012) SMN1 gene duplications are associated with sporadic ALS. Neurology 78: 776\u2010780","journal-title":"Neurology"},{"key":"BFEMMM201202303_CR6","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1083\/jcb.200906113","volume":"186","author":"CS Bond","year":"2009","unstructured":"Bond CS, Fox AH (2009) Paraspeckles: nuclear bodies built on long noncoding RNA. J Cell Biol 186: 637\u2010644","journal-title":"J Cell Biol"},{"key":"BFEMMM201202303_CR7","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1093\/hmg\/ddq508","volume":"20","author":"N Boulisfane","year":"2011","unstructured":"Boulisfane N, Choleza M, Rage F, Neel H, Soret J, Bordonne R (2011) Impaired minor tri\u2010snRNP assembly generates differential splicing defects of U12\u2010type introns in lymphoblasts derived from a type I SMA patient. Hum Mol Genet 20: 641\u2010648","journal-title":"Hum Mol Genet"},{"key":"BFEMMM201202303_CR8","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1093\/emboj\/20.7.1774","volume":"20","author":"E Buratti","year":"2001","unstructured":"Buratti E, Dork T, Zuccato E, Pagani F, Romano M, Baralle FE (2001) Nuclear factor TDP\u201043 and SR proteins promote in vitro and in vivo CFTR exon 9 skipping. EMBO J 20: 1774\u20101784","journal-title":"EMBO J"},{"key":"BFEMMM201202303_CR9","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/nrn2670","volume":"10","author":"AH Burghes","year":"2009","unstructured":"Burghes AH, Beattie CE (2009) Spinal muscular atrophy: why do low levels of survival motor neuron protein make motor neurons sick? Nat Rev Neurosci 10: 597\u2010609","journal-title":"Nat Rev Neurosci"},{"key":"BFEMMM201202303_CR10","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s00401-007-0237-2","volume":"114","author":"NJ Cairns","year":"2007","unstructured":"Cairns NJ, Bigio EH, Mackenzie IR, Neumann M, Lee VM, Hatanpaa KJ, White CL III, Schneider JA, Grinberg LT, Halliday G, et al (2007) Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol 114: 5\u201022","journal-title":"Acta Neuropathol"},{"key":"BFEMMM201202303_CR11","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.jsb.2009.06.006","volume":"167","author":"I Casafont","year":"2009","unstructured":"Casafont I, Bengoechea R, Tapia O, Berciano MT, Lafarga M (2009) TDP\u201043 localizes in mRNA transcription and processing sites in mammalian neurons. J Struct Biol 167: 235\u2010241","journal-title":"J Struct Biol"},{"key":"BFEMMM201202303_CR12","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/nrneurol.2010.18","volume":"6","author":"AS Chen\u2010Plotkin","year":"2010","unstructured":"Chen\u2010Plotkin AS, Lee VM, Trojanowski JQ (2010) TAR DNA\u2010binding protein 43 in neurodegenerative disease. Nat Rev Neurol 6: 211\u2010220","journal-title":"Nat Rev Neurol"},{"key":"BFEMMM201202303_CR13","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.cell.2009.02.011","volume":"136","author":"TA Cooper","year":"2009","unstructured":"Cooper TA, Wan L, Dreyfuss G (2009) RNA and disease. Cell 136: 777\u2010793","journal-title":"Cell"},{"key":"BFEMMM201202303_CR14","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1093\/hmg\/6.8.1205","volume":"6","author":"DD Coovert","year":"1997","unstructured":"Coovert DD, Le TT, McAndrew PE, Strasswimmer J, Crawford TO, Mendell JR, Coulson SE, Androphy EJ, Prior TW, Burghes AH (1997) The survival motor neuron protein in spinal muscular atrophy. Hum Mol Genet 6: 1205\u20101214","journal-title":"Hum Mol Genet"},{"key":"BFEMMM201202303_CR15","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1212\/01.wnl.0000233830.85206.1e","volume":"67","author":"P Corcia","year":"2006","unstructured":"Corcia P, Camu W, Halimi JM, Vourc'h P, Antar C, Vedrine S, Giraudeau B, de Toffol B, Andres CR (2006) SMN1 gene, but not SMN2, is a risk factor for sporadic ALS. Neurology 67: 1147\u20101150","journal-title":"Neurology"},{"key":"BFEMMM201202303_CR16","doi-asserted-by":"crossref","first-page":"4116","DOI":"10.1093\/nar\/gkp342","volume":"37","author":"A D'Ambrogio","year":"2009","unstructured":"D'Ambrogio A, Buratti E, Stuani C, Guarnaccia C, Romano M, Ayala YM, Baralle FE (2009) Functional mapping of the interaction between TDP\u201043 and hnRNP A2 in vivo. Nucleic Acids Res 37: 4116\u20104126","journal-title":"Nucleic Acids Res"},{"key":"BFEMMM201202303_CR17","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/nrg2680","volume":"10","author":"PA Dion","year":"2009","unstructured":"Dion PA, Daoud H, Rouleau GA (2009) Genetics of motor neuron disorders: new insights into pathogenic mechanisms. Nat Rev Genet 10: 769\u2010782","journal-title":"Nat Rev Genet"},{"key":"BFEMMM201202303_CR18","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/nature07677","volume":"457","author":"AD Ebert","year":"2009","unstructured":"Ebert AD, Yu J, Rose FF, Jr, Mattis VB, Lorson CL, Thomson JA, Svendsen CN (2009) Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature 457: 277\u2010280","journal-title":"Nature"},{"key":"BFEMMM201202303_CR19","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/emboj.2009.324","volume":"29","author":"FC Fiesel","year":"2010","unstructured":"Fiesel FC, Voigt A, Weber SS, Van den Haute C, Waldenmaier A, Gorner K, Walter M, Anderson ML, Kern JV, Rasse TM, et al (2010) Knockdown of transactive response DNA\u2010binding protein (TDP\u201043) downregulates histone deacetylase 6. EMBO J 29: 209\u2010221","journal-title":"EMBO J"},{"key":"BFEMMM201202303_CR20","doi-asserted-by":"crossref","first-page":"e921","DOI":"10.1371\/journal.pone.0000921","volume":"2","author":"F Gabanella","year":"2007","unstructured":"Gabanella F, Butchbach ME, Saieva L, Carissimi C, Burghes AH, Pellizzoni L (2007) Ribonucleoprotein assembly defects correlate with spinal muscular atrophy severity and preferentially affect a subset of spliceosomal snRNPs. PLoS One 2: e921","journal-title":"PLoS One"},{"key":"BFEMMM201202303_CR21","doi-asserted-by":"crossref","first-page":"37908","DOI":"10.1074\/jbc.274.53.37908","volume":"274","author":"T Giesemann","year":"1999","unstructured":"Giesemann T, Rathke\u2010Hartlieb S, Rothkegel M, Bartsch JW, Buchmeier S, Jockusch BM, Jockusch H (1999) A role for polyproline motifs in the spinal muscular atrophy protein SMN. Profilins bind to and colocalize with smn in nuclear gems. J Biol Chem 274: 37908\u201037914","journal-title":"J Biol Chem"},{"key":"BFEMMM201202303_CR22","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1083\/jcb.200702036","volume":"179","author":"J Huang","year":"2007","unstructured":"Huang J, Furuya A, Furuichi T (2007) Very\u2010KIND, a KIND domain containing RasGEF, controls dendrite growth by linking Ras small GTPases and MAP2. J Cell Biol 179: 539\u2010552","journal-title":"J Cell Biol"},{"key":"BFEMMM201202303_CR23","doi-asserted-by":"crossref","first-page":"3421","DOI":"10.1093\/hmg\/dds174","volume":"21","author":"S Kariya","year":"2012","unstructured":"Kariya S, Re DB, Jacquier A, Nelson K, Przedborski S, Monani UR (2012) Mutant superoxide dismutase 1 (SOD1), a cause of amyotrophic lateral sclerosis, disrupts the recruitment of SMN, the spinal muscular atrophy protein to nuclear Cajal bodies. Hum Mol Genet 21: 3421\u20103434","journal-title":"Hum Mol Genet"},{"key":"BFEMMM201202303_CR24","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1177\/0883073807305666","volume":"22","author":"SJ Kolb","year":"2007","unstructured":"Kolb SJ, Battle DJ, Dreyfuss G (2007) Molecular functions of the SMN complex. J Child Neurol 22: 990\u2010994","journal-title":"J Child Neurol"},{"key":"BFEMMM201202303_CR25","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.cell.2008.03.004","volume":"132","author":"RI Kumaran","year":"2008","unstructured":"Kumaran RI, Thakar R, Spector DL (2008) Chromatin dynamics and gene positioning. Cell 132: 929\u2010934","journal-title":"Cell"},{"key":"BFEMMM201202303_CR26","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/j.cell.2009.03.006","volume":"136","author":"C Lagier\u2010Tourenne","year":"2009","unstructured":"Lagier\u2010Tourenne C, Cleveland DW (2009) Rethinking ALS: the FUS about TDP\u201043. Cell 136: 1001\u20101004","journal-title":"Cell"},{"key":"BFEMMM201202303_CR27","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/nrn3121","volume":"13","author":"EB Lee","year":"2012","unstructured":"Lee EB, Lee VM, Trojanowski JQ (2012) Gains or losses: molecular mechanisms of TDP43\u2010mediated neurodegeneration. Nat Rev Neurosci 13: 38\u201050","journal-title":"Nat Rev Neurosci"},{"key":"BFEMMM201202303_CR28","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.tins.2010.02.003","volume":"33","author":"R Lemmens","year":"2010","unstructured":"Lemmens R, Moore MJ, Al\u2010Chalabi A, Brown RH, Jr, Robberecht W (2010) RNA metabolism and the pathogenesis of motor neuron diseases. Trends Neurosci 33: 249\u2010258","journal-title":"Trends Neurosci"},{"key":"BFEMMM201202303_CR29","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.tig.2011.05.006","volume":"27","author":"YS Mao","year":"2011","unstructured":"Mao YS, Zhang B, Spector DL (2011) Biogenesis and function of nuclear bodies. Trends Genet 27: 295\u2010306","journal-title":"Trends Genet"},{"key":"BFEMMM201202303_CR30","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1126\/science.1134108","volume":"314","author":"M Neumann","year":"2006","unstructured":"Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T, Grossman M, Clark CM, et al (2006) Ubiquitinated TDP\u201043 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314: 130\u2010133","journal-title":"Science"},{"key":"BFEMMM201202303_CR31","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1093\/hmg\/ddg084","volume":"12","author":"T Okuda","year":"2003","unstructured":"Okuda T, Hattori H, Takeuchi S, Shimizu J, Ueda H, Palvimo JJ, Kanazawa I, Kawano H, Nakagawa M, Okazawa H (2003) PQBP\u20101 transgenic mice show a late\u2010onset motor neuron disease\u2010like phenotype. Hum Mol Genet 12: 711\u2010725","journal-title":"Hum Mol Genet"},{"key":"BFEMMM201202303_CR32","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1126\/science.1074962","volume":"298","author":"L Pellizzoni","year":"2002","unstructured":"Pellizzoni L, Yong J, Dreyfuss G (2002) Essential role for the SMN complex in the specificity of snRNP assembly. Science 298: 1775\u20101779","journal-title":"Science"},{"key":"BFEMMM201202303_CR33","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/nn.2779","volume":"14","author":"M Polymenidou","year":"2011","unstructured":"Polymenidou M, Lagier\u2010Tourenne C, Hutt KR, Huelga SC, Moran J, Liang TY, Ling SC, Sun E, Wancewicz E, Mazur C, et al (2011) Long pre\u2010mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP\u201043. Nat Neurosci 14: 459\u2010468","journal-title":"Nat Neurosci"},{"key":"BFEMMM201202303_CR34","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1093\/hmg\/ddp498","volume":"19","author":"SJ Rabin","year":"2010","unstructured":"Rabin SJ, Kim JM, Baughn M, Libby RT, Kim YJ, Fan Y, La Spada A, Stone B, Ravits J (2010) Sporadic ALS has compartment\u2010specific aberrant exon splicing and altered cell\u2010matrix adhesion biology. Hum Mol Genet 19: 313\u2010328","journal-title":"Hum Mol Genet"},{"key":"BFEMMM201202303_CR35","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1074\/jbc.M110.190884","volume":"286","author":"CF Sephton","year":"2011","unstructured":"Sephton CF, Cenik C, Kucukural A, Dammer EB, Cenik B, Han Y, Dewey CM, Roth FP, Herz J, Peng J, et al (2011) Identification of neuronal RNA targets of TDP\u201043\u2010containing ribonucleoprotein complexes. J Biol Chem 286: 1204\u20101215","journal-title":"J Biol Chem"},{"key":"BFEMMM201202303_CR36","doi-asserted-by":"crossref","first-page":"16325","DOI":"10.1073\/pnas.1003459107","volume":"107","author":"X Shan","year":"2010","unstructured":"Shan X, Chiang PM, Price DL, Wong PC (2010) Altered distributions of Gemini of coiled bodies and mitochondria in motor neurons of TDP\u201043 transgenic mice. Proc Natl Acad Sci USA 107: 16325\u201016330","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMMM201202303_CR37","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.cell.2008.05.002","volume":"133","author":"K Talbot","year":"2008","unstructured":"Talbot K, Davies KE (2008) Is good housekeeping the key to motor neuron survival? Cell 133: 572\u2010574","journal-title":"Cell"},{"key":"BFEMMM201202303_CR38","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/nn.2778","volume":"14","author":"JR Tollervey","year":"2011","unstructured":"Tollervey JR, Curk T, Rogelj B, Briese M, Cereda M, Kayikci M, Konig J, Hortobagyi T, Nishimura AL, Zupunski V, et al (2011) Characterizing the RNA targets and position\u2010dependent splicing regulation by TDP\u201043. Nat Neurosci 14: 452\u2010458","journal-title":"Nat Neurosci"},{"key":"BFEMMM201202303_CR39","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1038\/nsmb.2185","volume":"18","author":"K Tripsianes","year":"2011","unstructured":"Tripsianes K, Madl T, Machyna M, Fessas D, Englbrecht C, Fischer U, Neugebauer KM, Sattler M (2011) Structural basis for dimethylarginine recognition by the Tudor domains of human SMN and SPF30 proteins. Nat Struct Mol Biol 18: 1414\u20101420","journal-title":"Nat Struct Mol Biol"},{"key":"BFEMMM201202303_CR40","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.conb.2008.09.018","volume":"18","author":"J Ule","year":"2008","unstructured":"Ule J (2008) Ribonucleoprotein complexes in neurologic diseases. Curr Opin Neurobiol 18: 516\u2010523","journal-title":"Curr Opin Neurobiol"},{"key":"BFEMMM201202303_CR41","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1212\/01.wnl.0000174472.03292.dd","volume":"65","author":"JH Veldink","year":"2005","unstructured":"Veldink JH, Kalmijn S, Van der Hout AH, Lemmink HH, Groeneveld GJ, Lummen C, Scheffer H, Wokke JH, Van den Berg LH (2005) SMN genotypes producing less SMN protein increase susceptibility to and severity of sporadic ALS. Neurology 65: 820\u2010825","journal-title":"Neurology"},{"key":"BFEMMM201202303_CR42","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1212\/WNL.56.6.749","volume":"56","author":"JH Veldink","year":"2001","unstructured":"Veldink JH, van den Berg LH, Cobben JM, Stulp RP, De Jong JM, Vogels OJ, Baas F, Wokke JH, Scheffer H (2001) Homozygous deletion of the survival motor neuron 2 gene is a prognostic factor in sporadic ALS. Neurology 56: 749\u2010752","journal-title":"Neurology"},{"key":"BFEMMM201202303_CR43","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.cell.2009.02.009","volume":"136","author":"MC Wahl","year":"2009","unstructured":"Wahl MC, Will CL, Luhrmann R (2009) The spliceosome: design principles of a dynamic RNP machine. Cell 136: 701\u2010718","journal-title":"Cell"},{"key":"BFEMMM201202303_CR44","doi-asserted-by":"crossref","first-page":"5543","DOI":"10.1128\/MCB.25.13.5543-5551.2005","volume":"25","author":"L Wan","year":"2005","unstructured":"Wan L, Battle DJ, Yong J, Gubitz AK, Kolb SJ, Wang J, Dreyfuss G (2005) The survival of motor neurons protein determines the capacity for snRNP assembly: biochemical deficiency in spinal muscular atrophy. Mol Cell Biol 25: 5543\u20105551","journal-title":"Mol Cell Biol"},{"key":"BFEMMM201202303_CR45","doi-asserted-by":"crossref","first-page":"13583","DOI":"10.1073\/pnas.212483099","volume":"99","author":"IF Wang","year":"2002","unstructured":"Wang IF, Reddy NM, Shen CK (2002) Higher order arrangement of the eukaryotic nuclear bodies. Proc Natl Acad Sci USA 99: 13583\u201013588","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMMM201202303_CR46","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1006\/bbrc.2000.2992","volume":"273","author":"M Waragai","year":"2000","unstructured":"Waragai M, Junn E, Kajikawa M, Takeuchi S, Kanazawa I, Shibata M, Mouradian MM, Okazawa H (2000) PQBP\u20101\/Npw38, a nuclear protein binding to the polyglutamine tract, interacts with U5\u201015kD\/dim1p via the carboxyl\u2010terminal domain. Biochem Biophys Res Commun 273: 592\u2010595","journal-title":"Biochem Biophys Res Commun"},{"key":"BFEMMM201202303_CR47","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nature11280","volume":"488","author":"CH Wu","year":"2012","unstructured":"Wu CH, Fallini C, Ticozzi N, Keagle PJ, Sapp PC, Piotrowska K, Lowe P, Koppers M, McKenna\u2010Yasek D, Baron DM, et al (2012) Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature 488: 499\u2010503","journal-title":"Nature"},{"key":"BFEMMM201202303_CR48","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.mcn.2011.02.013","volume":"47","author":"S Xiao","year":"2011","unstructured":"Xiao S, Sanelli T, Dib S, Sheps D, Findlater J, Bilbao J, Keith J, Zinman L, Rogaeva E, Robertson J (2011) RNA targets of TDP\u201043 identified by UV\u2010CLIP are deregulated in ALS. Mol Cell Neurosci 47: 167\u2010180","journal-title":"Mol Cell Neurosci"},{"key":"BFEMMM201202303_CR49","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.celrep.2012.08.025","volume":"2","author":"T Yamazaki","year":"2012","unstructured":"Yamazaki T, Chen S, Yu Y, Yan B, Haertlein TC, Carrasco MA, Tapia JC, Zhai B, Das R, Lalancette\u2010Hebert M, et al (2012) FUS\u2010SMN protein interactions link the motor neuron diseases ALS and SMA. Cell Rep 2: 799\u2010806","journal-title":"Cell Rep"},{"key":"BFEMMM201202303_CR50","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.cell.2008.03.031","volume":"133","author":"Z Zhang","year":"2008","unstructured":"Zhang Z, Lotti F, Dittmar K, Younis I, Wan L, Kasim M, Dreyfuss G (2008) SMN deficiency causes tissue\u2010specific perturbations in the repertoire of snRNAs and widespread defects in splicing. Cell 133: 585\u2010600","journal-title":"Cell"}],"container-title":["EMBO Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1002\/emmm.201202303.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/emmm.201202303","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1002\/emmm.201202303\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.embopress.org\/doi\/pdf\/10.1002\/emmm.201202303","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1002\/emmm.201202303.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T06:07:06Z","timestamp":1779084426000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1002\/emmm.201202303"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,1,25]]},"references-count":50,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2013,2,1]]}},"alternative-id":["BFEMMM201202303"],"URL":"https:\/\/doi.org\/10.1002\/emmm.201202303","relation":{},"ISSN":["1757-4676","1757-4684"],"issn-type":[{"value":"1757-4676","type":"print"},{"value":"1757-4684","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,1,25]]},"assertion":[{"value":"28 November 2012","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 December 2012","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 December 2012","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 January 2013","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}