{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:30:35Z","timestamp":1790796635926,"version":"4.1.0"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,6,8]],"date-time":"2018-06-08T00:00:00Z","timestamp":1528416000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,6,8]],"date-time":"2018-06-08T00:00:00Z","timestamp":1528416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mutations in multiple RNA\/DNA binding proteins cause Amyotrophic Lateral Sclerosis (ALS). Included among these are the three members of the FET family (FUS, EWSR1 and TAF15) and the structurally similar MATR3. Here, we characterized the interactomes of these four proteins, revealing that they largely have unique interactors, but share in common an association with U1 snRNP. The latter observation led us to analyze the interactome of the U1 snRNP machinery. Surprisingly, this analysis revealed the interactome contains ~220 components, and of these, &gt;200 are shared with the RNA polymerase II (RNAP II) machinery. Among the shared components are multiple ALS and Spinal muscular Atrophy (SMA)-causative proteins and numerous discrete complexes, including the SMN complex, transcription factor complexes, and RNA processing complexes. Together, our data indicate that the RNAP II\/U1 snRNP machinery functions in a wide variety of molecular pathways, and these pathways are candidates for playing roles in ALS\/SMA pathogenesis.<\/jats:p>","DOI":"10.1038\/s41598-018-27136-3","type":"journal-article","created":{"date-parts":[[2018,6,4]],"date-time":"2018-06-04T09:23:45Z","timestamp":1528104225000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Interactome analyses revealed that the U1 snRNP machinery overlaps extensively with the RNAP II machinery and contains multiple ALS\/SMA-causative proteins"],"prefix":"10.1038","volume":"8","author":[{"given":"Binkai","family":"Chi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy D.","family":"O\u2019Connell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Yamazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaya","family":"Gangopadhyay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven P.","family":"Gygi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Reed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,6,8]]},"reference":[{"key":"27136_CR1","doi-asserted-by":"publisher","first-page":"2548","DOI":"10.1172\/JCI82693","volume":"125","author":"OM Peters","year":"2015","unstructured":"Peters, O. M., Ghasemi, M. & Brown, R. H. Jr. Emerging mechanisms of molecular pathology in ALS. The Journal of clinical investigation 125, 2548, https:\/\/doi.org\/10.1172\/JCI82693 (2015).","journal-title":"The Journal of clinical investigation"},{"key":"27136_CR2","doi-asserted-by":"publisher","unstructured":"Jovicic, A., Paul, J. W., III & Gitler, A. D. Nuclear transport dysfunction: a common theme in amyotrophic lateral sclerosis and frontotemporal dementia. Journal of neurochemistry, https:\/\/doi.org\/10.1111\/jnc.13642 (2016).","DOI":"10.1111\/jnc.13642"},{"key":"27136_CR3","doi-asserted-by":"publisher","unstructured":"Gao, F. B., Almeida, S. & Lopez-Gonzalez, R. Dysregulated molecular pathways in amyotrophic lateral sclerosis-frontotemporal dementia spectrum disorder. EMBO J, https:\/\/doi.org\/10.15252\/embj.201797568 (2017).","DOI":"10.15252\/embj.201797568"},{"key":"27136_CR4","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1038\/nrneurol.2015.57","volume":"11","author":"X Paez-Colasante","year":"2015","unstructured":"Paez-Colasante, X., Figueroa-Romero, C., Sakowski, S. A., Goutman, S. A. & Feldman, E. L. Amyotrophic lateral sclerosis: mechanisms and therapeutics in the epigenomic era. Nat Rev Neurol 11, 266\u2013279, https:\/\/doi.org\/10.1038\/nrneurol.2015.57 (2015).","journal-title":"Nat Rev Neurol"},{"key":"27136_CR5","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/nature20413","volume":"539","author":"JP Taylor","year":"2016","unstructured":"Taylor, J. P., Brown, R. H. Jr. & Cleveland, D. W. Decoding ALS: from genes to mechanism. Nature 539, 197\u2013206, https:\/\/doi.org\/10.1038\/nature20413 (2016).","journal-title":"Nature"},{"key":"27136_CR6","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1083\/jcb.201302044","volume":"201","author":"YR Li","year":"2013","unstructured":"Li, Y. R., King, O. D., Shorter, J. & Gitler, A. D. Stress granules as crucibles of ALS pathogenesis. The Journal of cell biology 201, 361\u2013372, https:\/\/doi.org\/10.1083\/jcb.201302044 (2013).","journal-title":"The Journal of cell biology"},{"key":"27136_CR7","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1126\/science.1166066","volume":"323","author":"TJ Kwiatkowski Jr.","year":"2009","unstructured":"Kwiatkowski, T. J. Jr. et al. Mutations in the FUS\/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 323, 1205\u20131208, https:\/\/doi.org\/10.1126\/science.1166066 (2009).","journal-title":"Science"},{"key":"27136_CR8","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1126\/science.1165942","volume":"323","author":"C Vance","year":"2009","unstructured":"Vance, C. et al. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323, 1208\u20131211, https:\/\/doi.org\/10.1126\/science.1165942 (2009).","journal-title":"Science"},{"key":"27136_CR9","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.1126\/science.1154584","volume":"319","author":"J Sreedharan","year":"2008","unstructured":"Sreedharan, J. et al. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319, 1668\u20131672, https:\/\/doi.org\/10.1126\/science.1154584 (2008).","journal-title":"Science"},{"key":"27136_CR10","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/S1474-4422(08)70071-1","volume":"7","author":"VM Van Deerlin","year":"2008","unstructured":"Van Deerlin, V. M. et al. TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histopathological analysis. Lancet neurology 7, 409\u2013416, https:\/\/doi.org\/10.1016\/S1474-4422(08)70071-1 (2008).","journal-title":"Lancet neurology"},{"key":"27136_CR11","doi-asserted-by":"publisher","unstructured":"Ratti, A. & Buratti, E. Physiological Functions and Pathobiology of TDP-43 and FUS\/TLS proteins. Journal of neurochemistry, https:\/\/doi.org\/10.1111\/jnc.13625 (2016).","DOI":"10.1111\/jnc.13625"},{"key":"27136_CR12","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1002\/ajmg.b.31158","volume":"156B","author":"N Ticozzi","year":"2011","unstructured":"Ticozzi, N. et al. Mutational analysis reveals the FUS homolog TAF15 as a candidate gene for familial amyotrophic lateral sclerosis. Am J Med Genet B Neuropsychiatr Genet 156B, 285\u2013290, https:\/\/doi.org\/10.1002\/ajmg.b.31158 (2011).","journal-title":"Am J Med Genet B Neuropsychiatr Genet"},{"key":"27136_CR13","doi-asserted-by":"publisher","first-page":"20881","DOI":"10.1073\/pnas.1109434108","volume":"108","author":"J Couthouis","year":"2011","unstructured":"Couthouis, J. et al. Feature Article: From the Cover: A yeast functional screen predicts new candidate ALS disease genes. Proc Natl Acad Sci USA 108, 20881\u201320890, https:\/\/doi.org\/10.1073\/pnas.1109434108 (2011).","journal-title":"Proc Natl Acad Sci USA"},{"key":"27136_CR14","doi-asserted-by":"publisher","first-page":"2899","DOI":"10.1093\/hmg\/dds116","volume":"21","author":"J Couthouis","year":"2012","unstructured":"Couthouis, J. et al. Evaluating the role of the FUS\/TLS-related gene EWSR1 in amyotrophic lateral sclerosis. Hum Mol Genet 21, 2899\u20132911, https:\/\/doi.org\/10.1093\/hmg\/dds116 (2012).","journal-title":"Hum Mol Genet"},{"key":"27136_CR15","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1038\/nn.3688","volume":"17","author":"JO Johnson","year":"2014","unstructured":"Johnson, J. O. et al. Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis. Nat Neurosci 17, 664\u2013666, https:\/\/doi.org\/10.1038\/nn.3688 (2014).","journal-title":"Nat Neurosci"},{"key":"27136_CR16","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1016\/j.neuron.2017.07.025","volume":"95","author":"IR Mackenzie","year":"2017","unstructured":"Mackenzie, I. R. et al. TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics. Neuron 95, 808\u2013816 e809, https:\/\/doi.org\/10.1016\/j.neuron.2017.07.025 (2017).","journal-title":"Neuron"},{"key":"27136_CR17","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1093\/jmcb\/mjp025","volume":"1","author":"AY Tan","year":"2009","unstructured":"Tan, A. Y. & Manley, J. L. The TET family of proteins: functions and roles in disease. J Mol Cell Biol 1, 82\u201392, https:\/\/doi.org\/10.1093\/jmcb\/mjp025 (2009).","journal-title":"J Mol Cell Biol"},{"key":"27136_CR18","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1146\/annurev-biochem-060614-034325","volume":"84","author":"JC Schwartz","year":"2015","unstructured":"Schwartz, J. C., Cech, T. R. & Parker, R. R. Biochemical Properties and Biological Functions of FET Proteins. Annual review of biochemistry 84, 355\u2013379, https:\/\/doi.org\/10.1146\/annurev-biochem-060614-034325 (2015).","journal-title":"Annual review of biochemistry"},{"key":"27136_CR19","doi-asserted-by":"publisher","first-page":"653","DOI":"10.15252\/embj.201489852","volume":"34","author":"MB Coelho","year":"2015","unstructured":"Coelho, M. B. et al. Nuclear matrix protein Matrin3 regulates alternative splicing and forms overlapping regulatory networks with PTB. EMBO J 34, 653\u2013668, https:\/\/doi.org\/10.15252\/embj.201489852 (2015).","journal-title":"EMBO J"},{"key":"27136_CR20","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1038\/nature11922","volume":"495","author":"HJ Kim","year":"2013","unstructured":"Kim, H. J. et al. Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature 495, 467\u2013473, https:\/\/doi.org\/10.1038\/nature11922 (2013).","journal-title":"Nature"},{"key":"27136_CR21","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1016\/j.neuron.2010.11.036","volume":"68","author":"JO Johnson","year":"2010","unstructured":"Johnson, J. O. et al. Exome sequencing reveals VCP mutations as a cause of familial ALS. Neuron 68, 857\u2013864, https:\/\/doi.org\/10.1016\/j.neuron.2010.11.036 (2010).","journal-title":"Neuron"},{"key":"27136_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5287","volume":"5","author":"V Boczonadi","year":"2014","unstructured":"Boczonadi, V. et al. EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia. Nature communications 5, 4287, https:\/\/doi.org\/10.1038\/ncomms5287 (2014).","journal-title":"Nature communications"},{"key":"27136_CR23","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1038\/ng1354","volume":"36","author":"OV Evgrafov","year":"2004","unstructured":"Evgrafov, O. V. et al. Mutant small heat-shock protein 27 causes axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy. Nature genetics 36, 602\u2013606, https:\/\/doi.org\/10.1038\/ng1354 (2004).","journal-title":"Nature genetics"},{"key":"27136_CR24","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1093\/hmg\/ddi452","volume":"15","author":"S Ackerley","year":"2006","unstructured":"Ackerley, S. et al. A mutation in the small heat-shock protein HSPB1 leading to distal hereditary motor neuronopathy disrupts neurofilament assembly and the axonal transport of specific cellular cargoes. Hum Mol Genet 15, 347\u2013354, https:\/\/doi.org\/10.1093\/hmg\/ddi452 (2006).","journal-title":"Hum Mol Genet"},{"key":"27136_CR25","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/j.ajhg.2016.01.006","volume":"98","author":"E Knierim","year":"2016","unstructured":"Knierim, E. et al. Mutations in Subunits of the Activating Signal Cointegrator 1 Complex Are Associated with Prenatal Spinal Muscular Atrophy and Congenital Bone Fractures. Am J Hum Genet 98, 473\u2013489, https:\/\/doi.org\/10.1016\/j.ajhg.2016.01.006 (2016).","journal-title":"Am J Hum Genet"},{"key":"27136_CR26","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12997","author":"J Oliveira","year":"2017","unstructured":"Oliveira, J., Martins, M., Pinto Leite, R., Sousa, M. & Santos, R. The new neuromuscular disease related with defects in the ASC-1 complex: report of a second case confirms ASCC1 involvement. Clinical genetics. https:\/\/doi.org\/10.1111\/cge.12997 (2017).","journal-title":"Clinical genetics"},{"key":"27136_CR27","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1038\/nature09479","volume":"468","author":"D Kaida","year":"2010","unstructured":"Kaida, D. et al. U1 snRNP protects pre-mRNAs from premature cleavage and polyadenylation. Nature 468, 664\u2013668, https:\/\/doi.org\/10.1038\/nature09479 (2010).","journal-title":"Nature"},{"key":"27136_CR28","doi-asserted-by":"publisher","first-page":"8608","DOI":"10.1073\/pnas.1506282112","volume":"112","author":"Y Yu","year":"2015","unstructured":"Yu, Y. & Reed, R. FUS functions in coupling transcription to splicing by mediating an interaction between RNAP II and U1 snRNP. Proc Natl Acad Sci USA 112, 8608\u20138613, https:\/\/doi.org\/10.1073\/pnas.1506282112 (2015).","journal-title":"Proc Natl Acad Sci USA"},{"key":"27136_CR29","doi-asserted-by":"publisher","DOI":"10.1038\/srep33996","volume":"6","author":"S Prpar Mihevc","year":"2016","unstructured":"Prpar Mihevc, S., Baralle, M., Buratti, E. & Rogelj, B. TDP-43 aggregation mirrors TDP-43 knockdown, affecting the expression levels of a common set of proteins. Scientific reports 6, 33996, https:\/\/doi.org\/10.1038\/srep33996 (2016).","journal-title":"Scientific reports"},{"key":"27136_CR30","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1093\/hmg\/11.1.93","volume":"11","author":"W Rossoll","year":"2002","unstructured":"Rossoll, W. et al. Specific interaction of Smn, the spinal muscular atrophy determining gene product, with hnRNP-R and gry-rbp\/hnRNP-Q: a role for Smn in RNA processing in motor axons? Hum Mol Genet 11, 93\u2013105 (2002).","journal-title":"Hum Mol Genet"},{"key":"27136_CR31","doi-asserted-by":"publisher","first-page":"5443","DOI":"10.1093\/emboj\/20.19.5443","volume":"20","author":"Z Mourelatos","year":"2001","unstructured":"Mourelatos, Z., Abel, L., Yong, J., Kataoka, N. & Dreyfuss, G. SMN interacts with a novel family of hnRNP and spliceosomal proteins. EMBO J 20, 5443\u20135452, https:\/\/doi.org\/10.1093\/emboj\/20.19.5443 (2001).","journal-title":"EMBO J"},{"key":"27136_CR32","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.4161\/cc.9.8.11298","volume":"9","author":"M Salton","year":"2010","unstructured":"Salton, M., Lerenthal, Y., Wang, S. Y., Chen, D. J. & Shiloh, Y. Involvement of Matrin 3 and SFPQ\/NONO in the DNA damage response. Cell Cycle 9, 1568\u20131576, https:\/\/doi.org\/10.4161\/cc.9.8.11298 (2010).","journal-title":"Cell Cycle"},{"key":"27136_CR33","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.neuron.2016.09.015","volume":"92","author":"R Lopez-Gonzalez","year":"2016","unstructured":"Lopez-Gonzalez, R. et al. Poly(GR) in C9ORF72-Related ALS\/FTD Compromises Mitochondrial Function and Increases Oxidative Stress and DNA Damage in iPSC-Derived Motor Neurons. Neuron 92, 383\u2013391, https:\/\/doi.org\/10.1016\/j.neuron.2016.09.015 (2016).","journal-title":"Neuron"},{"key":"27136_CR34","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1038\/ng.3626","volume":"48","author":"KP Kenna","year":"2016","unstructured":"Kenna, K. P. et al. NEK1 variants confer susceptibility to amyotrophic lateral sclerosis. Nature genetics 48, 1037\u20131042, https:\/\/doi.org\/10.1038\/ng.3626 (2016).","journal-title":"Nature genetics"},{"key":"27136_CR35","doi-asserted-by":"publisher","first-page":"E7701","DOI":"10.1073\/pnas.1611673113","volume":"113","author":"SJ Hill","year":"2016","unstructured":"Hill, S. J. et al. Two familial ALS proteins function in prevention\/repair of transcription-associated DNA damage. Proc Natl Acad Sci USA 113, E7701\u2013E7709, https:\/\/doi.org\/10.1073\/pnas.1611673113 (2016).","journal-title":"Proc Natl Acad Sci USA"},{"key":"27136_CR36","doi-asserted-by":"publisher","first-page":"290","DOI":"10.3389\/fncel.2016.00290","volume":"10","author":"J Higelin","year":"2016","unstructured":"Higelin, J. et al. FUS Mislocalization and Vulnerability to DNA Damage in ALS Patients Derived hiPSCs and Aging Motoneurons. Frontiers in cellular neuroscience 10, 290, https:\/\/doi.org\/10.3389\/fncel.2016.00290 (2016).","journal-title":"Frontiers in cellular neuroscience"},{"key":"27136_CR37","doi-asserted-by":"publisher","first-page":"2882","DOI":"10.1093\/hmg\/ddx170","volume":"26","author":"MA Farg","year":"2017","unstructured":"Farg, M. A., Konopka, A., Soo, K. Y., Ito, D. & Atkin, J. D. The DNA damage response (DDR) is induced by the C9orf72 repeat expansion in amyotrophic lateral sclerosis. Hum Mol Genet 26, 2882\u20132896, https:\/\/doi.org\/10.1093\/hmg\/ddx170 (2017).","journal-title":"Hum Mol Genet"},{"key":"27136_CR38","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1038\/nn.4604","volume":"20","author":"C Walker","year":"2017","unstructured":"Walker, C. et al. C9orf72 expansion disrupts ATM-mediated chromosomal break repair. Nat Neurosci 20, 1225\u20131235, https:\/\/doi.org\/10.1038\/nn.4604 (2017).","journal-title":"Nat Neurosci"},{"key":"27136_CR39","doi-asserted-by":"publisher","first-page":"E2347","DOI":"10.1073\/pnas.1613181114","volume":"114","author":"M Jangi","year":"2017","unstructured":"Jangi, M. et al. SMN deficiency in severe models of spinal muscular atrophy causes widespread intron retention and DNA damage. Proc Natl Acad Sci USA 114, E2347\u2013E2356, https:\/\/doi.org\/10.1073\/pnas.1613181114 (2017).","journal-title":"Proc Natl Acad Sci USA"},{"key":"27136_CR40","doi-asserted-by":"publisher","first-page":"8973","DOI":"10.1093\/nar\/gkv809","volume":"43","author":"J Bizarro","year":"2015","unstructured":"Bizarro, J. et al. NUFIP and the HSP90\/R2TP chaperone bind the SMN complex and facilitate assembly of U4-specific proteins. Nucleic Acids Res 43, 8973\u20138989, https:\/\/doi.org\/10.1093\/nar\/gkv809 (2015).","journal-title":"Nucleic Acids Res"},{"key":"27136_CR41","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15615","volume":"8","author":"P Cloutier","year":"2017","unstructured":"Cloutier, P. et al. R2TP\/Prefoldin-like component RUVBL1\/RUVBL2 directly interacts with ZNHIT2 to regulate assembly of U5 small nuclear ribonucleoprotein. Nature communications 8, 15615, https:\/\/doi.org\/10.1038\/ncomms15615 (2017).","journal-title":"Nature communications"},{"key":"27136_CR42","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1038\/nature10925","volume":"484","author":"P Close","year":"2012","unstructured":"Close, P. et al. DBIRD complex integrates alternative mRNA splicing with RNA polymerase II transcript elongation. Nature 484, 386\u2013389, https:\/\/doi.org\/10.1038\/nature10925 (2012).","journal-title":"Nature"},{"key":"27136_CR43","doi-asserted-by":"publisher","first-page":"E1111","DOI":"10.1073\/pnas.1620293114","volume":"114","author":"KY Shi","year":"2017","unstructured":"Shi, K. Y. et al. Toxic PRn poly-dipeptides encoded by the C9orf72 repeat expansion block nuclear import and export. Proc Natl Acad Sci USA 114, E1111\u2013E1117, https:\/\/doi.org\/10.1073\/pnas.1620293114 (2017).","journal-title":"Proc Natl Acad Sci USA"},{"key":"27136_CR44","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1038\/nn.4085","volume":"18","author":"A Jovicic","year":"2015","unstructured":"Jovicic, A. et al. Modifiers of C9orf72 dipeptide repeat toxicity connect nucleocytoplasmic transport defects to FTD\/ALS. Nat Neurosci 18, 1226\u20131229, https:\/\/doi.org\/10.1038\/nn.4085 (2015).","journal-title":"Nat Neurosci"},{"key":"27136_CR45","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/nature14973","volume":"525","author":"K Zhang","year":"2015","unstructured":"Zhang, K. et al. The C9orf72 repeat expansion disrupts nucleocytoplasmic transport. Nature 525, 56\u201361, https:\/\/doi.org\/10.1038\/nature14973 (2015).","journal-title":"Nature"},{"key":"27136_CR46","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-14924-6","volume":"7","author":"A Boehringer","year":"2017","unstructured":"Boehringer, A. et al. ALS Associated Mutations in Matrin 3 Alter Protein-Protein Interactions and Impede mRNA Nuclear Export. Scientific reports 7, 14529, https:\/\/doi.org\/10.1038\/s41598-017-14924-6 (2017).","journal-title":"Scientific reports"},{"key":"27136_CR47","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1152\/physiolgenomics.00087.2001","volume":"16","author":"F Dangond","year":"2004","unstructured":"Dangond, F. et al. Molecular signature of late-stage human ALS revealed by expression profiling of postmortem spinal cord gray matter. Physiol Genomics 16, 229\u2013239, https:\/\/doi.org\/10.1152\/physiolgenomics.00087.2001 (2004).","journal-title":"Physiol Genomics"},{"key":"27136_CR48","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1046\/j.0305-1846.2001.00332.x","volume":"27","author":"S Sathasivam","year":"2001","unstructured":"Sathasivam, S., Ince, P. G. & Shaw, P. J. Apoptosis in amyotrophic lateral sclerosis: a review of the evidence. Neuropathology and applied neurobiology 27, 257\u2013274 (2001).","journal-title":"Neuropathology and applied neurobiology"},{"key":"27136_CR49","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/nature10353","volume":"477","author":"HX Deng","year":"2011","unstructured":"Deng, H. X. et al. Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS\/dementia. Nature 477, 211\u2013215, https:\/\/doi.org\/10.1038\/nature10353 (2011).","journal-title":"Nature"},{"key":"27136_CR50","doi-asserted-by":"publisher","first-page":"239 e211","DOI":"10.1016\/j.neurobiolaging.2017.06.018","volume":"58","author":"E Teyssou","year":"2017","unstructured":"Teyssou, E. et al. Novel UBQLN2 mutations linked to amyotrophic lateral sclerosis and atypical hereditary spastic paraplegia phenotype through defective HSP70-mediated proteolysis. Neurobiol Aging 58, 239 e211\u2013239 e220, https:\/\/doi.org\/10.1016\/j.neurobiolaging.2017.06.018 (2017).","journal-title":"Neurobiol Aging"},{"key":"27136_CR51","doi-asserted-by":"publisher","first-page":"4241","DOI":"10.1002\/j.1460-2075.1991.tb05002.x","volume":"10","author":"W Keller","year":"1991","unstructured":"Keller, W., Bienroth, S., Lang, K. M. & Christofori, G. Cleavage and polyadenylation factor CPF specifically interacts with the pre-mRNA 3\u2019 processing signal AAUAAA. EMBO J 10, 4241\u20134249 (1991).","journal-title":"EMBO J"},{"key":"27136_CR52","doi-asserted-by":"publisher","first-page":"2672","DOI":"10.1101\/gad.9.21.2672","volume":"9","author":"KG Murthy","year":"1995","unstructured":"Murthy, K. G. & Manley, J. L. The 160-kD subunit of human cleavage-polyadenylation specificity factor coordinates pre-mRNA 3\u2032-end formation. Genes & development 9, 2672\u20132683 (1995).","journal-title":"Genes & development"},{"key":"27136_CR53","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1038\/nature05363","volume":"444","author":"CR Mandel","year":"2006","unstructured":"Mandel, C. R. et al. Polyadenylation factor CPSF-73 is the pre-mRNA 3\u2032-end-processing endonuclease. Nature 444, 953\u2013956, https:\/\/doi.org\/10.1038\/nature05363 (2006).","journal-title":"Nature"},{"key":"27136_CR54","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.cell.2012.05.029","volume":"150","author":"MG Berg","year":"2012","unstructured":"Berg, M. G. et al. U1 snRNP determines mRNA length and regulates isoform expression. Cell 150, 53\u201364, https:\/\/doi.org\/10.1016\/j.cell.2012.05.029 (2012).","journal-title":"Cell"},{"key":"27136_CR55","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1101\/gad.1397406","volume":"20","author":"R Das","year":"2006","unstructured":"Das, R. et al. Functional coupling of RNAP II transcription to spliceosome assembly. Genes & development 20, 1100\u20131109 (2006).","journal-title":"Genes & development"},{"key":"27136_CR56","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1016\/j.molcel.2007.05.036","volume":"26","author":"R Das","year":"2007","unstructured":"Das, R. et al. SR Proteins Function in Coupling RNAP II Transcription to Pre-mRNA Splicing. Molecular cell 26, 867\u2013881, https:\/\/doi.org\/10.1016\/j.molcel.2007.05.036 (2007).","journal-title":"Molecular cell"},{"key":"27136_CR57","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1038\/414929a","volume":"414","author":"YW Fong","year":"2001","unstructured":"Fong, Y. W. & Zhou, Q. Stimulatory effect of splicing factors on transcriptional elongation. Nature 414, 929\u2013933 (2001).","journal-title":"Nature"},{"key":"27136_CR58","doi-asserted-by":"publisher","first-page":"1512","DOI":"10.1101\/gad.1302205","volume":"19","author":"S Masuda","year":"2005","unstructured":"Masuda, S. et al. Recruitment of the human TREX complex to mRNA during splicing. Genes & development 19, 1512\u20131517 (2005).","journal-title":"Genes & development"},{"key":"27136_CR59","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1016\/j.cell.2006.10.044","volume":"127","author":"H Cheng","year":"2006","unstructured":"Cheng, H. et al. Human mRNA export machinery recruited to the 5\u2032 end of mRNA. Cell 127, 1389\u20131400 (2006).","journal-title":"Cell"},{"key":"27136_CR60","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1093\/nar\/11.5.1475","volume":"11","author":"JD Dignam","year":"1983","unstructured":"Dignam, J. D., Lebovitz, R. M. & Roeder, R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res 11, 1475\u20131489 (1983).","journal-title":"Nucleic Acids Res"},{"key":"27136_CR61","doi-asserted-by":"publisher","first-page":"7469","DOI":"10.1021\/ac301572t","volume":"84","author":"GC McAlister","year":"2012","unstructured":"McAlister, G. C. et al. Increasing the multiplexing capacity of TMTs using reporter ion isotopologues with isobaric masses. Analytical chemistry 84, 7469\u20137478, https:\/\/doi.org\/10.1021\/ac301572t (2012).","journal-title":"Analytical chemistry"},{"issue":"1","key":"27136_CR62","doi-asserted-by":"publisher","first-page":"30 31","DOI":"10.1002\/cpbi.5","volume":"54","author":"G Stelzer","year":"2016","unstructured":"Stelzer, G. et al. The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses. Curr Protoc Bioinformatics 54(1), 30 31\u201331 30 33, https:\/\/doi.org\/10.1002\/cpbi.5 (2016).","journal-title":"Curr Protoc Bioinformatics"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-27136-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-27136-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-27136-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T06:15:41Z","timestamp":1671603341000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-27136-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,8]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["27136"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-27136-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,8]]},"assertion":[{"value":"12 April 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 May 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 June 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"8755"}}